Differentiated Thyroid Cancer (DTC), Osteosarcoma, Solid Malignant Tumors, Tumors
Conditions
Keywords
E7080, Lenvatinib, Solid malignancies, Osteosarcoma, Differentiated Thyroid Cancer
Brief summary
This is a phase 1/2 study evaluating safety, tolerability, and efficacy of lenvatinib as single-agent, and in combination with chemotherapy (ifosfamide and etoposide) in children and adolescents with refractory or relapsed solid malignancies including differentiated thyroid carcinoma (single agent lenvatinib) and osteosarcoma (single agent and combination lenvatinib).
Detailed description
The study consists of 5 cohorts: Cohort 1 (Single-Agent Dose-Finding) dose-escalation to find the recommended dose (RD) of lenvatinib using time-to-event continual reassessment method (TiTE-CRM) in children and adolescents with relapsed or refractory solid malignant tumors. When the RD is identified, Cohorts 2A, 2B, and 3A will enroll in parallel. Cohort 2 (Single-Agent Expansion) will evaluate the efficacy of lenvatinib at the RD in children, adolescents, and young adults with 1. 131 iodine-refractory differentiated thyroid cancer (DTC) \[Cohort 2A\] or 2. Relapsed or refractory osteosarcoma \[Cohort 2B\] Cohort 3A (Combination Dose-Finding) will determine the RD of lenvatinib in combination with ifosfamide and etoposide in children, adolescents, and young adults with relapsed or refractory osteosarcoma. Cohort 3B (Combination Expansion) will evaluate the efficacy of lenvatinib at the RD from Cohort 3A in combination with ifosfamide and etoposide in children, adolescents, and young adults with relapsed or refractory osteosarcoma. Participants with osteosarcoma who have enrolled into Cohort 1 or 2B and experienced progressive disease will also be candidates for enrollment in Cohort 3B. Lenvatinib will be provided as hard capsules containing 1, 4, or 10 mg lenvatinib. Lenvatinib capsules should be dissolved in water or apple juice for those who are unable to swallow capsules.
Interventions
DRUGLenvatinib
Cohort 1: Lenvatinib will be administered orally, once daily on Days 1 to 28 of each 28-day cycle at a starting dose of 11 mg/m2. Dose can be de-escalated to 9 mg/m2 or escalated to 14 and 17 mg/m2.
DRUGIfosfamide
Ifosfamide 3000 mg/m2/day (starting dose) will be administered on Days 1 to 3 of each 21-day cycle for a total of 5 cycles. Ifosfamide dose can be de-escalated to 2400 mg/m2/day and 1800 mg/m2/day.
DRUGEtoposide
Etoposide 100 mg/m2/day (starting dose) will be administered on Days 1 to 3 of each 21-day cycle for a total of 5 cycles. Etoposide dose can be de-escalated to 80 mg/m2/day and 60 mg/m2/day.
Sponsors
Merck Sharp & Dohme LLC
Eisai Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed diagnosis of solid malignant tumor. 1. Cohort 1: Any solid malignant tumor. 2. Cohort 2A: Differentiated Thyroid Cancer (DTC) with one of the following histological subtypes: i) Papillary thyroid cancer (PTC). i.a) Follicular variant. i.b) Other variants (including but not limited to tall cell, columnar cell, cribriform-morular, solid, oxyphil, Warthin's-like, trabecular, tumor with nodular fasciitis-like stroma, Hurthle cell variant of papillary carcinoma, or poorly differentiated carcinomas). ii) Follicular thyroid cancer (FTC). ii.a) Hurthle cell. ii.b) Clear cell. ii.c) Insular. c) Cohort 2B, 3A, and 3B: Relapsed or refractory osteosarcoma. 2. Relapsed or refractory solid tumor malignancy that has progressed on standard anticancer therapy with no available curative options. (Note: Osteosarcoma participants must be in first or subsequent relapse \[greater than or equal to first relapse\]). Only the osteosarcoma participants enrolled to Cohorts 3A and 3B must be deemed candidates for ifosfamide and etoposide chemotherapy). 3. Evaluable or measurable disease that meets the following criteria: 1. Participants must have evaluable or measurable disease based on RECIST 1.1 using computed tomography (CT)/magnetic resonance imaging (MRI). 2. Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must have subsequently grown unequivocally to be deemed a target lesion. 4. DTC participants must be 131 iodine-refractory/ relapsed as defined by at least one of the following: 1. One or more evaluable or measurable lesions that do not demonstrate iodine uptake on any radioiodine scan; or 2. One or more evaluable or measurable lesions that have progressed based on RECIST 1.1, within 12 months of 131 iodine therapy, despite demonstration of radioiodine avidity at the time of that treatment by pre- or post-treatment scanning. These participants must not be eligible for possible curative surgery; or 3. Cumulative activity of 131 iodine greater than 400 millicuries (mCi) or 14.8 gigabecquerels (GBq), with the last dose administered at least 6 months prior to study entry. 5. Participants with DTC must be receiving thyroxine suppression therapy and levels of thyroid stimulating hormone (TSH) should not be elevated (TSH should be less than or equal to 5.50 milliunits per liter (mU/L)). When tolerated by the participant, thyroxine dose should be changed to achieve TSH suppression (TSH less than 0.50 mU/L). 6. Participants with known central nervous system (CNS) primary tumors or metastases who have completed brain therapy (such as radiotherapy, stereotactic radiosurgery, or surgical resection) and have remained clinically stable, asymptomatic, and off of steroids for 2 weeks prior to Cycle 1 Day 1 will be eligible. 7. Male or female participants age 2 years to less than18 years and less than or equal to 25 years for osteosarcoma subjects at the time of informed consent. 8. Lansky play score greater than or equal to 50% or Karnofsky Performance Status score greater than or equal to 50%. Use Karnofsky for participants greater than or equal to 16 years of age and Lansky for participants less than 16 years of age. 9. Life expectancy greater than or equal to 3 months. 10. Adequate bone marrow function as evidenced by: 1. absolute neutrophil count (ANC) greater than or equal to 1.0 x 10\^9/L (for Cohorts 3A and 3B leucocyte count greater than or equal to 2 x 10\^9/L; participants with bone marrow involvement should have ANC greater than or equal to 0.8 x 10\^9/L and leucocyte count greater than or equal to 1 x 10\^9/L). 2. hemoglobin greater than or equal to 8.0 grams/deciliter (g/dL) (a hemoglobin less than 8.0 g/dL is acceptable if it is corrected by growth factor or transfusion before starting lenvatinib). 3. platelet count greater than or equal to 75 x 10\^9/L. 11. Adequate liver function as evidenced by: 1. bilirubin less than or equal 1.5 times the upper limit of normal (ULN). 2. alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 times ULN. 12. Adequate renal function as evidenced by: a) Serum creatinine based on age/gender as below. If serum creatinine is greater than maximum serum creatinine for age/gender as shown in the table below, then creatinine clearance (or radioisotope glomerular filtration rate \[GFR\]) must be greater than 70 milliliter/minute/1.73 square meter (mL/min/1.73 m2). Maximum Serum Creatinine in milligrams/deciliter (mg/dL) for male: i. Age 2 to less than 6 years = 0.8 ii. Age 6 to less than 10 years = 1.0 iii. Age 10 to less than 13 years = 1.2 iv. Age 13 to less than 16 years = 1.5 v. Age greater than or equal to 16 years = 1.7 Maximum Serum Creatinine (mg/dL) for Female: vi. Age 2 to less than 6 years = 0.8 vii. Age 6 to less than 10 years = 1.0 viii. Age 10 to less than 13 years = 1.2 ix. Age 13 to less than 16 years = 1.4 x. Age greater than or equal to 16 years = 1.4 The threshold creatinine values in this Table were derived from the Schwartz formula for estimating glomerular filtration rate using child length and stature data published by the CDC. b) Urine dipstick less than 2+ for proteinuria. Participants who have greater than or equal to 2+ proteinuria on dipstick urinalysis should undergo a spot protein-creatinine (P/C) ratio that should be Grade less than 2. c) No clinical evidence of nephrotic syndrome. 13. Adequate cardiac function as evidenced by left ventricular ejection fraction (LVEF) greater than or equal to 50%) at baseline as determined by echocardiography. 14. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as: BP less than 95th percentile for sex, age, and height/length at screening (as per National Heart Lung and Blood Institute guidelines) and no change in antihypertensive medications within 1-week prior to Cycle 1/Day 1. Osteosarcoma subjects 18 to 25 years should have BP ≤150/90 mm Hg at screening and no change in antihypertensive therapy within 1 week prior to Cycle 1/Day 1. 15. Washout of 3 weeks in case of prior chemotherapy, 6 weeks if treatment included nitrosoureas; 4 weeks for definitive radiotherapy, and 2 weeks for palliative radiotherapy; 3 months from high-dose chemotherapy and stem cell rescue; 3 weeks from major surgery. Participants must have recovered from the acute toxic effects of all prior anticancer therapy before enrollment into the study. 16. Written and signed informed consent from the parent(s) or legal representative (guardian) and assent from the minor participant. Written informed consent from subjects ≥18 years. 17. Willing and able to comply with the protocol, scheduled follow-up, and management of toxicity as judged by the Investigator. Cohort 3B (Combination Expansion): Osteosarcoma subjects who progressed in Cohorts 1 or 2B and opt to receive combination therapy. 18. Osteosarcoma participants receiving combination therapy of lenvatinib with ifosfamide and etoposide should meet only Inclusion Criteria Numbers 6 through 17 (after progression in Cohort 2B).
Exclusion criteria
1. Any active infection or infectious illness unless fully recovered prior to dosing. 2. Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study. 3. Other organ toxicity due to prior anticancer therapy (investigational agent, chemotherapy, or radiation therapy) except alopecia, and ototoxicity due to cisplatin not already covered in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 1: Recommended Dose (RD) of Lenvatinib | Cycle 1 (28 days) | RD was defined as the dose that had a dose limiting toxicity (DLT) rate closest to the targeted 20% rate. DLT was an adverse drug reaction and was assessed according to common terminology criteria for adverse events (CTCAE) version (v) 4.03 defined as 1) Grade 4 neutropenia for greater than or equal to (\>=) 7 days, 2) Grade \>=3 thrombocytopenia with bleeding, or lasting greater than (\>) 7 days, 3) Grade \>=3 febrile neutropenia, 4) Next course of chemotherapy delayed for \>=7 days, 5) Grade \>=3 non-hematologic toxicity persisting \>7 days optimal supportive care, 6) Grade 4 hypertension, confirmed systolic or diastolic blood pressure \>25 millimeters of mercury (mmHg) above the 95th percentile for age, or an elevated diastolic blood pressure (that is, \>95th percentile for age) not controlled by a single antihypertensive medication within 14 days of use, 7) Grade 3 proteinuria, 8) Any recurrent Grade 2 non-hematological toxicity requiring \>=2 interruption and dose reductions. |
| Cohort 2A: Number of Participants With Objective Response (OR) of Complete Response (CR) or Partial Response (PR) | From date of first dose of study drug until first documentation of PD or death, whichever occurred first (until the data cut-off date, 31 May 2019) | OR was defined as participants with best overall response (BOR) of CR or PR as assessed by investigator based on response evaluation criteria in solid tumors (RECIST) version (v) 1.1. For OR, the BOR was defined as the best response (CR or PR for \>4 weeks) recorded from the start of the treatment until PD or death whichever occurred first. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. |
| Cohort 2A: Number of Participants With Best Overall Response (BOR) | From first dose of study drug until PD or death, whichever occurred first (until the data cut-off date, 31 May 2019) | BOR was defined as the best response of CR or PR for \>4 weeks or SD for \>=7 weeks recorded from the start of the treatment until PD or death, whichever occurred first based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. |
| Cohorts 2B and 3B: Progression-free Survival (PFS) Rate at Month 4 | At Month 4 | Progression free survival at Month 4 (PFS-4) rate was defined as the percentage of participants who were alive and without PD at Month 4 after the first dose of study drug, based on RECIST v1.1, using a binomial proportion with corresponding 95% confidence interval (CI). PD: \>= 20% increase in sum of diameters of target lesions, reference-smallest sum recorded in study (sum at baseline if that was smallest). Sum of diameters must have absolute increase of \>=5 mm. Appearance of \>=1 new lesions also considered PD. |
| Cohort 3A: Recommended Dose (RD) of Lenvatinib When Given in Combination With Etoposide and Ifosfamide | Cycle 1 (21 days) | RD of lenvatinib when given in combination with ifosfamide and etoposide was defined as dose that resulted in no more than 1 DLT per 6 participants,or hematologic DLT in 1 participant and nonhematologic DLT in another participant per 6 participants,upon repeating same dose level.DLT was adverse drug reaction and assessed per CTCAE v4.03 defined as 1)Grade 4 neutropenia for \>=10 days,2)Grade \>=3 thrombocytopenia with bleeding,or lasting \>=10 days,3)Grade \>=3 febrile neutropenia lasting \>=7 days,4)Next course of chemotherapy delayed for \>=7 days,5)Grade \>=3 nonhematologic toxicity persisting \>7 days despite optimal supportive care,6)Grade 4 hypertension,confirmed systolic or diastolic blood pressure \>25 mmHg above 95th percentile for age,or elevated diastolic blood pressure(\>95th percentile for age)not controlled by single antihypertensive medication within 14 days use,7)Grade 3 proteinuria,8)Any recurrent Grade 2 nonhematological toxicity requiring \>=2 interruption and dose reductions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohorts 1, 2A, 2B, 3A and 3B: Progression-free Survival (PFS) | From first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019) | PFS was defined as the time (in months) from the date of first dose of study drug to the date of first documentation of PD or date of death, whichever occurred first, based on RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the baseline SOD of target lesions. 95% CI of median were calculated according to Brookmeyer and Crowley method. |
| Cohorts 1, 2A, 2B, 3A and 3B: Time to Progression (TTP) | From first dose of study drug until PD (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019) | TTP was defined as the time from the date of first dose of study drug to the date of first documentation of PD based on RECIST 1.1. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the baseline SOD of target lesions. 95% CI of median were calculated according to Brookmeyer and Crowley method. |
| Cohorts 1, 2A, 2B, 3A and 3B: Overall Survival (OS) | From first dose of study drug until death (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019) | OS was defined as the time from the date of the first dose of study drug until the date of death from any cause. Participants who are lost to follow-up and those who are alive at the date of data cutoff were censored at the date the participant was last known to be alive (or the data cutoff date). 95% CI of median were calculated according to Brookmeyer and Crowley method. |
| Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From the date of first dose of study drug up to 30 days after the last dose (up to approximately 7 years) | Number of participants with TEAEs (serious and non-serious adverse events) and SAEs were reported based on their safety assessments of hematology, clinical chemistry, proximal tibial growth, fecal occult blood, physical examinations, regular measurement of vital signs and electrocardiogram parameter values. |
| Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline up to approximately 4 years 7 months | An aliquot of the urine samples were collected to analyze protein by dipstick method, microscopic examination (if protein was abnormal). The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters of urine protein can be read as negative, Trace, plus (+) 1, +2, +3 and +4 indicating proportional concentrations in the urine sample. The plus sign increases with a higher level of proteins in the urine. |
| Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | From date of first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019) | BOR: best response of CR or PR for \>4 weeks or SD for \>=7 weeks from first dose, recorded from start of treatment until PD or death, whichever occurred first based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have reduction in their short axis \<10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD was defined as: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Not evaluable (NE) means BOR of NE or SD of \<7 weeks duration. Unknown means no data were available on the case report form. |
| Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline up to approximately 4 years 7 months | KPS: compare effectiveness of medicine for disease and assess outcomes in participants. KPS Scores: recorded on 11 point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90 and 100%), where 0=Dead; 10=moribund, fatal processes progressing rapidly; 20=very sick, hospital admission necessary, active supportive treatment necessary; 30=severely disabled, hospital admission is indicated although death not imminent; 40=disabled, requires special care/assistance; 50=requires considerable assistance/frequent medical care; 60=requires occasional assistance, but is able to care for personal needs; 70=cares for self, unable to carry normal activity or active work; 80=normal activity with effort, some signs of disease; 90=able to carry on normal activity, minor signs of disease; 100=normal no complaints, no evidence of disease. Lower score, worse survival for most serious illnesses. |
| Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cohorts 1, 2A, 2B: Cycle(C)1 Day(D)1: 0.5-4 hours (h), 6-10 h post-dose, C1D15: pre-dose, 0.5-4 h, 6-10 h post-dose, C2D1: pre-dose, 2-12 h post-dose; Cohorts 3A, 3B: C1D1: 0.5-4 h, 6-10 h post-dose, C2D1: pre-dose, 2-12 h post-dose | Duration of each cycle for Cohorts 1, 2A, 2B is 28 days. Duration of each cycle for Cohorts 3A, 3B is 21 days. |
| Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | Cohort 2B: Baseline, Cycle 2-3 Day 1 (Duration of each cycle=28 days); Cohort 3B: Baseline, Cycle 2 Day 1, Cycle 4 Day 1 (Duration of each cycle=21 days) | Serum biomarkers included Fibroblast Growth Factor (FGF) 19, FGF 21, Vascular Endothelial Growth Factor (VEGF). In this outcome measure, percent change from baseline in serum biomarkers level per PFS-4, Yes and PFS-4, No have been reported. As per assessment of investigator based on RECIST v1.1, PFS-4, Yes= participants evaluable for PFS-4 month and alive and without PD at 4 months from the first dose, PFS-4, No=participants evaluable for PFS-4 month and not alive or with PD at 4 months from the first dose. |
| Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | First dose of study drug until 30 days after last dose of study drug (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019) | TEAEs (serious and non-serious), those occurred most frequently have been reported in this outcome measure. Palmar-plantar E syndrome refers to Palmar-plantar erythrodysaesthesia syndrome. |
| Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Cycle 1 Day 1 (Cycle length=28 days for Cohorts 1, 2A, 2B; Cycle length=21 days for Cohorts 3A, 3B) | In acceptability questionnaire, participants were asked to answer the overall acceptability of lenvatinib suspension considering the following elements: taste, appearance, smell and how does it feel in the mouth. Overall acceptability was answered in terms of 7 responses: Super good, really good, good, may be good or may be bad, bad, really bad, super bad. Overall acceptability was the overall acceptance for taste, appearance, smell, and the feeling in mouth. In this measure, number of participants have been reported per their overall acceptability responses. |
| Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline up to approximately 4 years 7 months | Lansky Performance Play Scale rates a child's activity level for \<16 years of age. Scores on scale range from 0 (unresponsive) to 100 ( fully active, normal), where 100=fully active, normal; 90=minor restrictions in physically strenuous activity; 80=active, but tires more quickly; 70=both greater restriction of and less time spent in play activity; 60=up and around, but minimal active play, keeps busy with quieter activities; 50=gets dressed, but lies around much of day, no active play, able to participant in quiet play and activities; 40=mostly in bed, participates in quiet activities; 30=in bed, needs assistance even for quiet play; 20=often sleeping, play entirely limited to very passive activities; 10=no play, does not get out of bed; 0=unresponsive. Higher score indicates more activity and lower indicates less or no activity. |
| Cohorts 1, 2B, 3A, and 3B: Objective Response Rate (ORR) | From date of first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019) | ORR was defined as the percentage of participants with a BOR of CR or PR for \>4 weeks or SD for \>=7 weeks as assessed by investigator based on RECIST v1.1, recorded from start of study treatment until PD or death whichever occurred first. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. 95% CI of the ORR were calculated according to Clopper and Pearson method. |
| Cohorts 1, 2A, 2B, 3A and 3B: Duration of Response (DOR) | First documentation of CR/PR until first documentation of PD (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019) | DOR was defined as time in months from the first documentation confirmed CR or PR until the first documentation of confirmed PD as assessed by investigator based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. 95% CI for the median were calculated according to Brookmeyer and Crowley method. |
| Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Who Experienced Disease Control | From first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019) | Participants were defined as having disease control if they had a BOR of CR or PR for \>4 weeks, or SD (minimum duration from first dose to SD \>=7 weeks) or if participants had a BOR of CR or Non-CR/Non-PD (minimum duration from first dose to Non-CR/Non-PD \>=7 weeks) per RECIST v1.1, recorded from first dose until PD or death whichever occurred first. CR: disappearance of all target/non-target lesions (non-lymph nodes). All pathological lymph nodes (target/non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest SOD. Non-CR/Non-PD: persistence of 1 or more non-target lesions, maintenance of tumor marker level above the normal limits. |
| Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Experienced Clinical Benefit | From first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019) | Participants were defined as having clinical benefit if they had a BOR of CR or PR for \>4 weeks or durable SD (lasting \>=23 weeks) or if participants had a BOR of CR or durable Non-CR/Non-PD (lasting \>=23 weeks) as per RECIST v1.1, recorded from first dose until PD or death whichever occurred first. CR: disappearance of all target/non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target/non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. Non-CR/Non-PD:persistence of 1 or more non-target lesions and maintenance of tumor marker level above the normal limits. |
Countries
France, Germany, Italy, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants took part at 19 investigative sites in France, Germany, Italy, Spain, United Kingdom and the United States. Total 117 participants were enrolled and screened, of which 20 participants were screen failures and 97 participants received study treatment.
Pre-assignment details
Prior to entering Cohort 1, some participants aged 2 to less than (\<) 6 years underwent a run-in period and received lenvatinib 5 milligram per square meter (mg/m\^2) per body surface area (BSA) as capsules or suspension once daily for 21 days.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 Participants (age group 2 to \<6 years and 6 to \<18 years) with relapsed or refractory solid malignant tumors received lenvatinib 11 mg/m\^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Eligible participants of age group 2 to \<6 years first underwent 21-days run-in period with lenvatinib 5 mg/m\^2, once daily before receiving lenvatinib 11 mg/m\^2 in Cycle 1 in Cohort 1. Duration of each treatment cycle in Cohort 1=28 days. After determining RD in Cohort 1, participants were enrolled in Cohorts 2A, 2B and 3A. | 3 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 Participants (age group 2 to \<6 years and 6 to \<18 years) with relapsed or refractory solid malignant tumors received lenvatinib 14 mg/m\^2 (per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as a single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by participant at any time, or study termination by sponsor, whichever occurred first. Eligible participants of age group 2 to \<6 years first underwent 21-days run-in period with lenvatinib 5 mg/m\^2, once daily before receiving lenvatinib 14 mg/m\^2 in Cycle 1 in Cohort 1. Duration of each treatment cycle in Cohort 1=28 days. After determining RD in Cohort 1, participants were enrolled in Cohorts 2A, 2B and 3A. | 9 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 Participants (of age group 6 to \<18 years) with relapsed or refractory solid malignant tumors received dose of lenvatinib 17 mg/m\^2 (administered per BSA, daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as a single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by the participant at any time, or study termination by the sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 1=28 days. After determining the RD in Cohort 1, participants were enrolled in Cohorts 2A, 2B and 3A. | 11 |
| Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 Participants with 131 iodine-refractory DTC received lenvatinib 14 mg/m\^2 (administered per BSA with daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as a single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by the participant at any time, or study termination by the sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 2A=28 days. | 1 |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 Participants with relapsed or refractory osteosarcoma received lenvatinib 14 mg/m\^2 (administered per BSA with daily dose capped at 24 mg/day) as capsule or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 28 of each treatment cycle as a single agent until PD, intolerable toxicity, participant noncompliance with safety or efficacy assessments, initiation of another anticancer therapy, voluntary discontinuation by the participant at any time, or study termination by the sponsor, whichever occurred first. Duration of each treatment cycle in Cohort 2B=28 days. | 31 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 Participants with relapsed or refractory osteosarcoma received lenvatinib 11 mg/m\^2 (20% lower than the RD from Cohort 1; administered per BSA with daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 21 of each treatment cycle in combination with ifosfamide 3000 mg/m\^2/day intravenously and etoposide 100 mg/m\^2/day intravenously on Days 1 to 3 of each treatment cycle for up to a total of 5 cycles as a combination therapy. Duration of each treatment cycle in Cohort 3A=21 days. After determining the RD in Cohort 3A, participants were enrolled in Cohort 3B. | 7 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 Participants with relapsed or refractory osteosarcoma received lenvatinib 14 mg/m\^2 (administrated per BSA with daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 21 of each treatment cycle in combination with ifosfamide 3000 mg/m\^2/day intravenously and etoposide 100 mg/m\^2/day intravenously on Days 1 to 3 of each treatment cycle for up to a total of 5 cycles as a combination therapy. Duration of each treatment cycle in Cohort 3A=21 days. After determining the RD in Cohort 3A, participants were enrolled in Cohort 3B. | 15 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 Participants with relapsed or refractory osteosarcoma received lenvatinib 14 mg/m\^2 (administrated per BSA with daily dose capped at 24 mg/day) as capsules or suspension (lenvatinib capsules were dissolved in water or apple juice for participants who were unable to swallow capsules and given as suspension), orally, once daily on Days 1 to 21 of each treatment cycle in combination with ifosfamide 3000 mg/m\^2/day intravenously and etoposide 100 mg/m\^2/day intravenously on Days 1 to 3 of each treatment cycle for up to a total of 5 cycles as a combination therapy. Duration of each treatment cycle in Cohort 3B=21 days. | 20 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 6 | 7 | 0 | 27 | 7 | 9 | 14 |
| Overall Study | Withdrawal of Consent | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Cohort 1, Single-agent Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohort 2A, Single-agent Expansion, DTC: Lenvatinib 14 mg/m^2 | Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18 to <=25 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 7 Participants | 2 Participants | 3 Participants | 5 Participants | 17 Participants |
| Age, Customized 2 to <6 years | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Age, Customized 6 to <18 years | 2 Participants | 8 Participants | 11 Participants | 1 Participants | 24 Participants | 5 Participants | 11 Participants | 15 Participants | 77 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 4 Participants | 1 Participants | 4 Participants | 3 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 4 Participants | 4 Participants | 0 Participants | 15 Participants | 5 Participants | 8 Participants | 10 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 5 Participants | 1 Participants | 12 Participants | 1 Participants | 3 Participants | 7 Participants | 34 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 7 Participants | 0 Participants | 9 Participants | 1 Participants | 1 Participants | 4 Participants | 27 Participants |
| Race (NIH/OMB) White | 2 Participants | 5 Participants | 3 Participants | 1 Participants | 20 Participants | 6 Participants | 14 Participants | 13 Participants | 64 Participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 5 Participants | 0 Participants | 18 Participants | 2 Participants | 5 Participants | 7 Participants | 43 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 6 Participants | 1 Participants | 13 Participants | 5 Participants | 10 Participants | 13 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 2 / 5 | 7 / 11 | 6 / 7 | 0 / 1 | 27 / 31 | 10 / 11 | 6 / 11 | 14 / 20 |
| other Total, other adverse events | 2 / 2 | 5 / 5 | 11 / 11 | 7 / 7 | 1 / 1 | 29 / 31 | 11 / 11 | 11 / 11 | 20 / 20 |
| serious Total, serious adverse events | 0 / 2 | 3 / 5 | 7 / 11 | 5 / 7 | 1 / 1 | 21 / 31 | 7 / 11 | 9 / 11 | 16 / 20 |
Outcome results
Primary
Cohort 1: Recommended Dose (RD) of Lenvatinib
RD was defined as the dose that had a dose limiting toxicity (DLT) rate closest to the targeted 20% rate. DLT was an adverse drug reaction and was assessed according to common terminology criteria for adverse events (CTCAE) version (v) 4.03 defined as 1) Grade 4 neutropenia for greater than or equal to (\>=) 7 days, 2) Grade \>=3 thrombocytopenia with bleeding, or lasting greater than (\>) 7 days, 3) Grade \>=3 febrile neutropenia, 4) Next course of chemotherapy delayed for \>=7 days, 5) Grade \>=3 non-hematologic toxicity persisting \>7 days optimal supportive care, 6) Grade 4 hypertension, confirmed systolic or diastolic blood pressure \>25 millimeters of mercury (mmHg) above the 95th percentile for age, or an elevated diastolic blood pressure (that is, \>95th percentile for age) not controlled by a single antihypertensive medication within 14 days of use, 7) Grade 3 proteinuria, 8) Any recurrent Grade 2 non-hematological toxicity requiring \>=2 interruption and dose reductions.
Time frame: Cycle 1 (28 days)
Population: Safety analysis set included all participants who received any study drug and had at least one post-baseline safety evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: All Participants | Cohort 1: Recommended Dose (RD) of Lenvatinib | 14 milligram per square meter (mg/m^2) |
Primary
Cohort 2A: Number of Participants With Best Overall Response (BOR)
BOR was defined as the best response of CR or PR for \>4 weeks or SD for \>=7 weeks recorded from the start of the treatment until PD or death, whichever occurred first based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Time frame: From first dose of study drug until PD or death, whichever occurred first (until the data cut-off date, 31 May 2019)
Population: Full analysis set included all enrolled participants who did not fail study screening.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: All Participants | Cohort 2A: Number of Participants With Best Overall Response (BOR) | Complete Response | 0 Participants |
| Cohort 1: All Participants | Cohort 2A: Number of Participants With Best Overall Response (BOR) | Partial Response | 1 Participants |
| Cohort 1: All Participants | Cohort 2A: Number of Participants With Best Overall Response (BOR) | Stable Disease | 0 Participants |
Primary
Cohort 2A: Number of Participants With Objective Response (OR) of Complete Response (CR) or Partial Response (PR)
OR was defined as participants with best overall response (BOR) of CR or PR as assessed by investigator based on response evaluation criteria in solid tumors (RECIST) version (v) 1.1. For OR, the BOR was defined as the best response (CR or PR for \>4 weeks) recorded from the start of the treatment until PD or death whichever occurred first. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Time frame: From date of first dose of study drug until first documentation of PD or death, whichever occurred first (until the data cut-off date, 31 May 2019)
Population: Full analysis set included all enrolled participants who did not fail study screening.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: All Participants | Cohort 2A: Number of Participants With Objective Response (OR) of Complete Response (CR) or Partial Response (PR) | 1 Participants |
Primary
Cohort 3A: Recommended Dose (RD) of Lenvatinib When Given in Combination With Etoposide and Ifosfamide
RD of lenvatinib when given in combination with ifosfamide and etoposide was defined as dose that resulted in no more than 1 DLT per 6 participants,or hematologic DLT in 1 participant and nonhematologic DLT in another participant per 6 participants,upon repeating same dose level.DLT was adverse drug reaction and assessed per CTCAE v4.03 defined as 1)Grade 4 neutropenia for \>=10 days,2)Grade \>=3 thrombocytopenia with bleeding,or lasting \>=10 days,3)Grade \>=3 febrile neutropenia lasting \>=7 days,4)Next course of chemotherapy delayed for \>=7 days,5)Grade \>=3 nonhematologic toxicity persisting \>7 days despite optimal supportive care,6)Grade 4 hypertension,confirmed systolic or diastolic blood pressure \>25 mmHg above 95th percentile for age,or elevated diastolic blood pressure(\>95th percentile for age)not controlled by single antihypertensive medication within 14 days use,7)Grade 3 proteinuria,8)Any recurrent Grade 2 nonhematological toxicity requiring \>=2 interruption and dose reductions.
Time frame: Cycle 1 (21 days)
Population: Safety analysis set included all participants who received any study drug and had at least one post-baseline safety evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: All Participants | Cohort 3A: Recommended Dose (RD) of Lenvatinib When Given in Combination With Etoposide and Ifosfamide | 14 milligram per square meter (mg/m^2) |
Primary
Cohorts 2B and 3B: Progression-free Survival (PFS) Rate at Month 4
Progression free survival at Month 4 (PFS-4) rate was defined as the percentage of participants who were alive and without PD at Month 4 after the first dose of study drug, based on RECIST v1.1, using a binomial proportion with corresponding 95% confidence interval (CI). PD: \>= 20% increase in sum of diameters of target lesions, reference-smallest sum recorded in study (sum at baseline if that was smallest). Sum of diameters must have absolute increase of \>=5 mm. Appearance of \>=1 new lesions also considered PD.
Time frame: At Month 4
Population: PFS-4 evaluable set included all participants treated with study drug for at least 4 months or those who died or radiologically progressed within 4 months after first dose, or received anticancer treatment within 4 months after first dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: All Participants | Cohorts 2B and 3B: Progression-free Survival (PFS) Rate at Month 4 | 32.1 percentage of participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 2B and 3B: Progression-free Survival (PFS) Rate at Month 4 | 66.7 percentage of participants |
Secondary
Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level
Serum biomarkers included Fibroblast Growth Factor (FGF) 19, FGF 21, Vascular Endothelial Growth Factor (VEGF). In this outcome measure, percent change from baseline in serum biomarkers level per PFS-4, Yes and PFS-4, No have been reported. As per assessment of investigator based on RECIST v1.1, PFS-4, Yes= participants evaluable for PFS-4 month and alive and without PD at 4 months from the first dose, PFS-4, No=participants evaluable for PFS-4 month and not alive or with PD at 4 months from the first dose.
Time frame: Cohort 2B: Baseline, Cycle 2-3 Day 1 (Duration of each cycle=28 days); Cohort 3B: Baseline, Cycle 2 Day 1, Cycle 4 Day 1 (Duration of each cycle=21 days)
Population: PFS-4 evaluable set: all participants treated with study drug for at least 4 months or those who died or radiologically progressed within 4 months after first dose or received anticancer treatment within 4 months after first dose. N: participants evaluable for this measure. n: participants who were evaluable for this measure for specific rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: All Participants | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C2D1: FGF 21 (PFS-4, No) | 134.3 percent change | Standard Deviation 203.81 |
| Cohort 1: All Participants | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C3D1: FGF 19 (PFS-4, Yes) | 47.3 percent change | Standard Deviation 130.42 |
| Cohort 1: All Participants | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C3D1: FGF 21 (PFS-4, Yes) | 55.0 percent change | Standard Deviation 125.51 |
| Cohort 1: All Participants | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C3D1: FGF 21 (PFS-4, No) | 17.0 percent change | Standard Deviation 88.92 |
| Cohort 1: All Participants | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C3D1: FGF 19 (PFS-4, No) | 194.5 percent change | Standard Deviation 180.71 |
| Cohort 1: All Participants | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C2D1: VEGF (PFS-4, Yes) | 119.9 percent change | Standard Deviation 309.01 |
| Cohort 1: All Participants | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C2D1: VEGF (PFS-4, No) | 124.2 percent change | Standard Deviation 212.18 |
| Cohort 1: All Participants | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C2D1: FGF 19 (PFS-4, No) | 109.9 percent change | Standard Deviation 139.19 |
| Cohort 1: All Participants | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C3D1: VEGF (PFS-4, Yes) | 64.3 percent change | Standard Deviation 153.5 |
| Cohort 1: All Participants | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C3D1: VEGF (PFS-4, No) | 23.2 percent change | Standard Deviation 69.67 |
| Cohort 1: All Participants | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C2D1: FGF 21 (PFS-4, Yes) | -14.9 percent change | Standard Deviation 68.95 |
| Cohort 1: All Participants | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C2D1: FGF 19 (PFS-4, Yes) | 48.7 percent change | Standard Deviation 110.78 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C4D1: VEGF (PFS-4, Yes) | 84.3 percent change | Standard Deviation 97.85 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C2D1: FGF 19 (PFS-4, Yes) | 172.1 percent change | Standard Deviation 211.86 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C2D1: FGF 19 (PFS-4, No) | 78.3 percent change | Standard Deviation 203.3 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C4D1: FGF 19 (PFS-4, Yes) | 237.7 percent change | Standard Deviation 204.94 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C4D1: FGF 19 (PFS-4, No) | 91.9 percent change | — |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C2D1: FGF 21 (PFS-4, Yes) | 70.2 percent change | Standard Deviation 138.9 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C2D1: FGF 21 (PFS-4, No) | 7.2 percent change | Standard Deviation 48.64 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C4D1: FGF 21 (PFS-4, Yes) | 256.2 percent change | Standard Deviation 323.34 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C2D1: VEGF (PFS-4, Yes) | 87.9 percent change | Standard Deviation 105.6 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C2D1: VEGF (PFS-4, No) | 95.8 percent change | Standard Deviation 92.53 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohort 2B, 3B: Percent Change From Baseline in Serum Biomarkers Level | C4D1: FGF 21 (PFS-4, No) | -1.5 percent change | — |
Comparison: C2D1: FGF 19 (PFS-4, Yes) vs. C2D1: FGF 19 (PFS-4, No)p-value: =0.20359Wilcoxon Rank-Sum Test
Comparison: C2D1: FGF 19 (PFS-4, Yes) vs. C2D1: FGF 19 (PFS-4, No)p-value: =0.50068Wilcoxon Rank-Sum Test
Comparison: C3D1: FGF 19 (PFS-4, Yes) vs. C3D1: FGF 19 (PFS-4, No)p-value: =0.05512Wilcoxon Rank-Sum Test
Comparison: C4D1: FGF 19 (PFS-4, Yes) vs. C4D1: FGF 19 (PFS-4, No)p-value: =0.50382Wilcoxon Rank-Sum Test
Comparison: C2D1: FGF 21 (PFS-4, Yes) vs. C2D1: FGF 21 (PFS-4, No)p-value: =0.0476Wilcoxon Rank-Sum Test
Comparison: C2D1: FGF 21 (PFS-4, Yes) vs. C2D1: FGF 21 (PFS-4, No)p-value: =0.2142Wilcoxon Rank-Sum Test
Comparison: C3D1: FGF 21 (PFS-4, Yes) vs. C3D1: FGF 21 (PFS-4, No)p-value: =0.42542Wilcoxon Rank-Sum Test
Comparison: C4D1: FGF 21 (PFS-4, Yes) vs. C4D1: FGF 21 (PFS-4, No)p-value: =0.73573Wilcoxon Rank-Sum Test
Comparison: C2D1: VEGF (PFS-4, Yes) vs. C2D1: VEGF (PFS-4, No)p-value: =0.35754Wilcoxon Rank-Sum Test
Comparison: C2D1: VEGF (PFS-4, Yes) vs. C2D1: VEGF (PFS-4, No)p-value: =0.59903Wilcoxon Rank-Sum Test
Comparison: C3D1: VEGF (PFS-4, Yes) vs. C3D1: VEGF (PFS-4, No)p-value: =1Wilcoxon Rank-Sum Test
Secondary
Cohorts 1, 2A, 2B, 3A and 3B: Duration of Response (DOR)
DOR was defined as time in months from the first documentation confirmed CR or PR until the first documentation of confirmed PD as assessed by investigator based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. 95% CI for the median were calculated according to Brookmeyer and Crowley method.
Time frame: First documentation of CR/PR until first documentation of PD (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
Population: Full analysis set included all enrolled participants who did not fail study screening. Here overall number of participants analyzed, N signifies participants who were evaluable for this measure. Here, N for Cohort 1 (Lenvatinib 11, 14, 17 mg/m\^2) and Cohort 3A (Lenvatinib 14 mg/m\^2) is zero as there were no events of CR or PR in these arms.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Duration of Response (DOR) | 1.9 months |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Duration of Response (DOR) | 4.6 months |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Duration of Response (DOR) | NA months |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Duration of Response (DOR) | NA months |
Secondary
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib
In acceptability questionnaire, participants were asked to answer the overall acceptability of lenvatinib suspension considering the following elements: taste, appearance, smell and how does it feel in the mouth. Overall acceptability was answered in terms of 7 responses: Super good, really good, good, may be good or may be bad, bad, really bad, super bad. Overall acceptability was the overall acceptance for taste, appearance, smell, and the feeling in mouth. In this measure, number of participants have been reported per their overall acceptability responses.
Time frame: Cycle 1 Day 1 (Cycle length=28 days for Cohorts 1, 2A, 2B; Cycle length=21 days for Cohorts 3A, 3B)
Population: Palatability analysis set included all participants who received oral suspension of lenvatinib and answered at least 1 question in the palatability questionnaire case report form.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Bad | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Really Bad | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Good | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Super Good | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Really Good | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | May be Good or May be Bad | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Super Bad | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Super Bad | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Bad | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Really Good | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Good | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | May be Good or May be Bad | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Super Good | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Really Bad | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Bad | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Super Bad | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | May be Good or May be Bad | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Really Good | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Super Good | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Really Bad | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Good | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | May be Good or May be Bad | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Super Bad | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Really Good | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Really Bad | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Good | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Super Good | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Bad | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | May be Good or May be Bad | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Super Good | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Really Good | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Good | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Bad | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Really Bad | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Super Bad | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | May be Good or May be Bad | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Super Bad | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Bad | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Good | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Really Bad | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Really Good | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Super Good | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Really Good | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Super Good | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Really Bad | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Bad | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Super Bad | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Good | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | May be Good or May be Bad | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Super Bad | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | May be Good or May be Bad | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Really Bad | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Super Good | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Good | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Bad | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Categorized Based on Overall Acceptability Questionnaire Responses for Suspension of Lenvatinib | Really Good | 0 Participants |
Secondary
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Experienced Clinical Benefit
Participants were defined as having clinical benefit if they had a BOR of CR or PR for \>4 weeks or durable SD (lasting \>=23 weeks) or if participants had a BOR of CR or durable Non-CR/Non-PD (lasting \>=23 weeks) as per RECIST v1.1, recorded from first dose until PD or death whichever occurred first. CR: disappearance of all target/non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target/non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. Non-CR/Non-PD:persistence of 1 or more non-target lesions and maintenance of tumor marker level above the normal limits.
Time frame: From first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
Population: Full analysis set included all enrolled participants who did not fail study screening.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Experienced Clinical Benefit | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Experienced Clinical Benefit | 3 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Experienced Clinical Benefit | 4 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Experienced Clinical Benefit | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Experienced Clinical Benefit | 7 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Experienced Clinical Benefit | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Experienced Clinical Benefit | 5 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Experienced Clinical Benefit | 8 Participants |
Secondary
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Who Experienced Disease Control
Participants were defined as having disease control if they had a BOR of CR or PR for \>4 weeks, or SD (minimum duration from first dose to SD \>=7 weeks) or if participants had a BOR of CR or Non-CR/Non-PD (minimum duration from first dose to Non-CR/Non-PD \>=7 weeks) per RECIST v1.1, recorded from first dose until PD or death whichever occurred first. CR: disappearance of all target/non-target lesions (non-lymph nodes). All pathological lymph nodes (target/non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest SOD. Non-CR/Non-PD: persistence of 1 or more non-target lesions, maintenance of tumor marker level above the normal limits.
Time frame: From first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
Population: Full analysis set included all enrolled participants who did not fail study screening.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Who Experienced Disease Control | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Who Experienced Disease Control | 5 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Who Experienced Disease Control | 5 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Who Experienced Disease Control | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Who Experienced Disease Control | 16 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Who Experienced Disease Control | 5 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Who Experienced Disease Control | 11 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants Who Experienced Disease Control | 14 Participants |
Secondary
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure
TEAEs (serious and non-serious), those occurred most frequently have been reported in this outcome measure. Palmar-plantar E syndrome refers to Palmar-plantar erythrodysaesthesia syndrome.
Time frame: First dose of study drug until 30 days after last dose of study drug (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
Population: Safety analysis set included all participants who received any study drug and had at least one post-baseline safety evaluation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Alanine aminotransferase increased | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypophosphataemia | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Abdominal pain | 2 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Neutropenia | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lymphocyte count decreased | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Abdominal pain upper | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Vomiting | 1 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Febrile neutropenia | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hyperhidrosis | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Fatigue | 2 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pyrexia | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Palmar-plantar E syndrome | 2 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypocalcaemia | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Diarrhea | 3 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Asthenia | 2 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Thrombocytopenia | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Wound dehiscence | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Neutrophil count decreased | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Stomatitis | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Erythema | 1 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | White blood cell count decreased | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pneumothorax | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypokalaemia | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oral dysaesthesia | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Anaemia | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Blood thyroid stimulating hormone increased | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dehydration | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Myalgia | 1 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Headache | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypothyroidism | 3 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Constipation | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dyspnoea | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Platelet count decreased | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Nausea | 1 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Decreased appetite | 3 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Insomnia | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dry skin | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Back pain | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Haematuria | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Arthralgia | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dizziness | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypertension | 2 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dysphonia | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pain in extremity | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hair color changes | 1 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hyperuricemia | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Epistaxis | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Toxic encephalopathy | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Leukopenia | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lymphopenia | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lethargy | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Weight decreased | 3 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypoalbuminaemia | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Haematochezia | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oral pain | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Proctalgia | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oropharyngeal pain | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Proteinuria | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Leukopenia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Insomnia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pain in extremity | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Febrile neutropenia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Thrombocytopenia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Epistaxis | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Weight decreased | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dizziness | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Proteinuria | 3 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Erythema | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hair color changes | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Arthralgia | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypocalcaemia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypertension | 3 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Haematuria | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Back pain | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dry skin | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pyrexia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oral pain | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Haematochezia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypoalbuminaemia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lymphopenia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lethargy | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oropharyngeal pain | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Proctalgia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Toxic encephalopathy | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Stomatitis | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hyperuricemia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | White blood cell count decreased | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Myalgia | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oral dysaesthesia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Abdominal pain | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Headache | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dysphonia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Abdominal pain upper | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Palmar-plantar E syndrome | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Diarrhea | 5 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dehydration | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Platelet count decreased | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Nausea | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Anaemia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lymphocyte count decreased | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dyspnoea | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Vomiting | 6 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hyperhidrosis | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Wound dehiscence | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Asthenia | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Fatigue | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Neutrophil count decreased | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypophosphataemia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Alanine aminotransferase increased | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypokalaemia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Blood thyroid stimulating hormone increased | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pneumothorax | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypothyroidism | 6 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Neutropenia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Decreased appetite | 5 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Constipation | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Nausea | 3 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Myalgia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Alanine aminotransferase increased | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Neutrophil count decreased | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Decreased appetite | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Platelet count decreased | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dyspnoea | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Diarrhea | 3 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Toxic encephalopathy | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lymphocyte count decreased | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Blood thyroid stimulating hormone increased | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Abdominal pain | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hair color changes | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Palmar-plantar E syndrome | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Erythema | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Weight decreased | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Thrombocytopenia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dysphonia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypothyroidism | 3 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypophosphataemia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Asthenia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Anaemia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pneumothorax | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Constipation | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Fatigue | 3 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Abdominal pain upper | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oral dysaesthesia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Vomiting | 3 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dehydration | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypokalaemia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | White blood cell count decreased | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypoalbuminaemia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Haematuria | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hyperhidrosis | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oropharyngeal pain | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lymphopenia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Febrile neutropenia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Wound dehiscence | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Insomnia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lethargy | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Arthralgia | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Leukopenia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Stomatitis | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pain in extremity | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Epistaxis | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Back pain | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypertension | 4 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Neutropenia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oral pain | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pyrexia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Proctalgia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Haematochezia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Proteinuria | 3 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hyperuricemia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypocalcaemia | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dizziness | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dry skin | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Headache | 1 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Haematuria | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Back pain | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pyrexia | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Stomatitis | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dry skin | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Arthralgia | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Haematochezia | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oral pain | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dehydration | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hyperuricemia | 1 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Headache | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypoalbuminaemia | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pain in extremity | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lethargy | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hyperhidrosis | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Febrile neutropenia | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Leukopenia | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | White blood cell count decreased | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oropharyngeal pain | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Erythema | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Neutropenia | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Wound dehiscence | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Proctalgia | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Proteinuria | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pneumothorax | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Neutrophil count decreased | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lymphocyte count decreased | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oral dysaesthesia | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Toxic encephalopathy | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Diarrhea | 1 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Nausea | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dizziness | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypocalcaemia | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Vomiting | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Asthenia | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Fatigue | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Alanine aminotransferase increased | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lymphopenia | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Blood thyroid stimulating hormone increased | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Weight decreased | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Constipation | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Decreased appetite | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypothyroidism | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Myalgia | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Thrombocytopenia | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dysphonia | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dyspnoea | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hair color changes | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Palmar-plantar E syndrome | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Epistaxis | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypertension | 1 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypokalaemia | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Abdominal pain | 1 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Anaemia | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypophosphataemia | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Platelet count decreased | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Insomnia | 1 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Abdominal pain upper | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Myalgia | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Haematuria | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Decreased appetite | 13 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Constipation | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Weight decreased | 6 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Blood thyroid stimulating hormone increased | 9 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Alanine aminotransferase increased | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lymphopenia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lymphocyte count decreased | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypokalaemia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Abdominal pain upper | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Anaemia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pneumothorax | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Haematochezia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Fatigue | 8 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Asthenia | 8 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oral dysaesthesia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypophosphataemia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Abdominal pain | 5 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Vomiting | 7 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Nausea | 8 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dizziness | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Insomnia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Diarrhea | 8 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Epistaxis | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Neutrophil count decreased | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dyspnoea | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dysphonia | 5 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Thrombocytopenia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Platelet count decreased | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Palmar-plantar E syndrome | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypothyroidism | 13 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hyperhidrosis | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Toxic encephalopathy | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypertension | 10 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dry skin | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oropharyngeal pain | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypoalbuminaemia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hyperuricemia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Stomatitis | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Erythema | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Arthralgia | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pyrexia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Proteinuria | 7 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hair color changes | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dehydration | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oral pain | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Wound dehiscence | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Proctalgia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | White blood cell count decreased | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypocalcaemia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lethargy | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Back pain | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Leukopenia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Headache | 5 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Neutropenia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Febrile neutropenia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pain in extremity | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oral pain | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Arthralgia | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Headache | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Proteinuria | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hair color changes | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Back pain | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dry skin | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dehydration | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypoalbuminaemia | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lethargy | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oropharyngeal pain | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Proctalgia | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hyperuricemia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Neutropenia | 6 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Febrile neutropenia | 5 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Stomatitis | 4 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | White blood cell count decreased | 4 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pyrexia | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Wound dehiscence | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hyperhidrosis | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Insomnia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypothyroidism | 5 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Abdominal pain | 6 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Diarrhea | 5 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Nausea | 7 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Vomiting | 5 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Asthenia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Fatigue | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Alanine aminotransferase increased | 3 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Blood thyroid stimulating hormone increased | 3 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Weight decreased | 5 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Decreased appetite | 4 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Myalgia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pain in extremity | 3 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dysphonia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Erythema | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Palmar-plantar E syndrome | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypertension | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Haematuria | 4 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypokalaemia | 4 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypophosphataemia | 3 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Platelet count decreased | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pneumothorax | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Leukopenia | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Neutrophil count decreased | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oral dysaesthesia | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Toxic encephalopathy | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lymphocyte count decreased | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Abdominal pain upper | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Anaemia | 9 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Epistaxis | 5 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Thrombocytopenia | 5 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Constipation | 5 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lymphopenia | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Haematochezia | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypocalcaemia | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dizziness | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dyspnoea | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oral pain | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Abdominal pain | 5 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Platelet count decreased | 3 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypophosphataemia | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypokalaemia | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Anaemia | 7 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Haematuria | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Palmar-plantar E syndrome | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Erythema | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypothyroidism | 6 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Epistaxis | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dysphonia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Headache | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lymphocyte count decreased | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Thrombocytopenia | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pain in extremity | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Decreased appetite | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Weight decreased | 3 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dyspnoea | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Constipation | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Blood thyroid stimulating hormone increased | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Alanine aminotransferase increased | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lymphopenia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Fatigue | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Haematochezia | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Asthenia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Vomiting | 6 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Febrile neutropenia | 3 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Nausea | 8 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dizziness | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oral dysaesthesia | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Diarrhea | 5 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Toxic encephalopathy | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Neutrophil count decreased | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Leukopenia | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pneumothorax | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Insomnia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hair color changes | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Abdominal pain upper | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Proctalgia | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Stomatitis | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oropharyngeal pain | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Myalgia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | White blood cell count decreased | 3 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lethargy | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypoalbuminaemia | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dehydration | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dry skin | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Back pain | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Arthralgia | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pyrexia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypertension | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hyperhidrosis | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Wound dehiscence | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypocalcaemia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Proteinuria | 5 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Neutropenia | 6 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hyperuricemia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dry skin | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Headache | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Back pain | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Erythema | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Febrile neutropenia | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypertension | 3 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Proctalgia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Proteinuria | 8 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oropharyngeal pain | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Myalgia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Abdominal pain upper | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pyrexia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oral dysaesthesia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lethargy | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypocalcaemia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Palmar-plantar E syndrome | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | White blood cell count decreased | 12 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hair color changes | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypoalbuminaemia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hyperuricemia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lymphopenia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dehydration | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Neutropenia | 8 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Blood thyroid stimulating hormone increased | 5 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Platelet count decreased | 11 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Constipation | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Insomnia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Diarrhea | 12 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypophosphataemia | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Alanine aminotransferase increased | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypokalaemia | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Lymphocyte count decreased | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hypothyroidism | 6 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Fatigue | 3 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Anaemia | 15 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Haematuria | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dyspnoea | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pneumothorax | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dizziness | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Hyperhidrosis | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Leukopenia | 3 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Epistaxis | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Dysphonia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Haematochezia | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Asthenia | 7 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Pain in extremity | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Abdominal pain | 6 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Vomiting | 12 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Thrombocytopenia | 5 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Wound dehiscence | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Stomatitis | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Arthralgia | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Decreased appetite | 5 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Oral pain | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Weight decreased | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Nausea | 13 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Toxic encephalopathy | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Most Frequent Treatment-emergent Adverse Events (TEAEs) Related to Lenvatinib Exposure | Neutrophil count decreased | 9 Participants |
Secondary
Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria
An aliquot of the urine samples were collected to analyze protein by dipstick method, microscopic examination (if protein was abnormal). The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters of urine protein can be read as negative, Trace, plus (+) 1, +2, +3 and +4 indicating proportional concentrations in the urine sample. The plus sign increases with a higher level of proteins in the urine.
Time frame: Baseline up to approximately 4 years 7 months
Population: Safety analysis set included all participants who received any study drug and had at least one post-baseline safety evaluation. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: Negative | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: Trace | 1 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: Negative | 2 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +1 | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: Negative | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +2, Worst Post baseline: Negative | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: Negative | 2 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: +1 | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: +2 | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: Trace | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +4, Worst Post baseline: Trace | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +4, Worst Post baseline: +1 | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: Trace | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +1 | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +2 | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +3 | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +1 | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +2 | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +3 | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: Trace | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +2 | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +3 | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +4 | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +4 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: Negative | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: Negative | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: Trace | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: Negative | 3 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: +2 | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: Trace | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +2 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +2 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: +1 | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +1 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +1 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: Negative | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +4, Worst Post baseline: Trace | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +4, Worst Post baseline: +1 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +2 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +3 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: Trace | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +2, Worst Post baseline: Negative | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: Trace | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +4 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +1 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +3 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +3 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +4 | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +2, Worst Post baseline: Negative | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: Trace | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +2 | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +1 | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +3 | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: Trace | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: Negative | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: Negative | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +2 | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: +1 | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: Negative | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: Trace | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: +2 | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +3 | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +4 | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: Trace | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +1 | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +2 | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +4 | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +4, Worst Post baseline: Trace | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +1 | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +4, Worst Post baseline: +1 | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: Negative | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +3 | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +2, Worst Post baseline: Negative | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: Negative | 1 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +3 | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: Trace | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +4 | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +2 | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +1 | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: Trace | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: Trace | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: Trace | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +3 | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: +1 | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +4, Worst Post baseline: +1 | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +4, Worst Post baseline: Trace | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +2 | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +4 | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +3 | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: Negative | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +1 | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: +2 | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: Negative | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +2 | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: Negative | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +1 | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +1 | 7 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +1 | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +3 | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: Negative | 4 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +2, Worst Post baseline: Negative | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: Negative | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: +1 | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: +2 | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: Trace | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +4, Worst Post baseline: Trace | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +4, Worst Post baseline: +1 | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +4 | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: Trace | 5 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +2 | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +3 | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +1 | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +2 | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +3 | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: Trace | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +4 | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +2 | 3 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: Negative | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: Trace | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: Negative | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +4 | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +4 | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: +2 | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +4, Worst Post baseline: +1 | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +2 | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +3 | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +1 | 7 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: Negative | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +1 | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +2 | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: +1 | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: Trace | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +3 | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +1 | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +3 | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +2, Worst Post baseline: Negative | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +4, Worst Post baseline: Trace | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: Negative | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: Trace | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: Trace | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: Negative | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +2 | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: Trace | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: Negative | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +1 | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +4, Worst Post baseline: +1 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: Trace | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +3 | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +4, Worst Post baseline: Trace | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +1 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: Trace | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +2 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: +2 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +4 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +3 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: +1 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +1 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: Trace | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: Negative | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +2 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +3 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +2, Worst Post baseline: Negative | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: Negative | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: Negative | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: Negative | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +4 | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: Trace | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +2 | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: +2 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +4, Worst Post baseline: +1 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +2, Worst Post baseline: Negative | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +4 | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +2 | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: Trace | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: Trace | 3 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: Negative | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +1 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: Trace | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: Negative | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +2 | 6 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +3 | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +3 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +4, Worst Post baseline: Trace | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: Trace | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: +1 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +3, Worst Post baseline: Negative | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +4 | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Trace, Worst Post baseline: +3 | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: Negative | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +1 | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: Negative, Worst Post baseline: +1 | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Measurements on Urine DipStick for Proteinuria | Baseline: +1, Worst Post baseline: +2 | 1 Participants |
Secondary
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores
KPS: compare effectiveness of medicine for disease and assess outcomes in participants. KPS Scores: recorded on 11 point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90 and 100%), where 0=Dead; 10=moribund, fatal processes progressing rapidly; 20=very sick, hospital admission necessary, active supportive treatment necessary; 30=severely disabled, hospital admission is indicated although death not imminent; 40=disabled, requires special care/assistance; 50=requires considerable assistance/frequent medical care; 60=requires occasional assistance, but is able to care for personal needs; 70=cares for self, unable to carry normal activity or active work; 80=normal activity with effort, some signs of disease; 90=able to carry on normal activity, minor signs of disease; 100=normal no complaints, no evidence of disease. Lower score, worse survival for most serious illnesses.
Time frame: Baseline up to approximately 4 years 7 months
Population: Safety analysis set included all participants who received any study drug and had at least one post-baseline safety evaluation. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 80%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 90% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:90% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:80% | 1 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:70% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score:100%, Worst Postbaseline score:100% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 70%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:80% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 80%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 90% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score:100%, Worst Postbaseline score:100% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 70%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:70% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:90% | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:90% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:80% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 70%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 80%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score:100%, Worst Postbaseline score:100% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:70% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 90% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 80%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 90% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score:100%, Worst Postbaseline score:100% | 1 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:80% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:70% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 70%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:90% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:90% | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score:100%, Worst Postbaseline score:100% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 80%, Worst Postbaseline score: 80% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 70% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:80% | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 80% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 70%, Worst Postbaseline score: 70% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:70% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 90% | 3 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 80%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 60% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:90% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score:100%, Worst Postbaseline score:100% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 90% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:70% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:80% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 70%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 80%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:70% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:80% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 90% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:90% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 70%, Worst Postbaseline score: 70% | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score:100%, Worst Postbaseline score:100% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 80% | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 80%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:70% | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 70%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 90% | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:80% | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score:100%, Worst Postbaseline score:100% | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 100%, Worst Postbaseline score:90% | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Karnofsky Performance Status (KPS) Scores | Baseline score: 90%, Worst Postbaseline score: 70% | 0 Participants |
Secondary
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score
Lansky Performance Play Scale rates a child's activity level for \<16 years of age. Scores on scale range from 0 (unresponsive) to 100 ( fully active, normal), where 100=fully active, normal; 90=minor restrictions in physically strenuous activity; 80=active, but tires more quickly; 70=both greater restriction of and less time spent in play activity; 60=up and around, but minimal active play, keeps busy with quieter activities; 50=gets dressed, but lies around much of day, no active play, able to participant in quiet play and activities; 40=mostly in bed, participates in quiet activities; 30=in bed, needs assistance even for quiet play; 20=often sleeping, play entirely limited to very passive activities; 10=no play, does not get out of bed; 0=unresponsive. Higher score indicates more activity and lower indicates less or no activity.
Time frame: Baseline up to approximately 4 years 7 months
Population: Safety analysis set included all participants who received any study drug and had at least one post-baseline safety evaluation. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score:100%, Worst Postbaseline score:90% | 3 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:80% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score:100%, Worst Postbaseline score:100% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 50% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:60% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 60%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 40% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:70% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 90% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score:100% | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 50% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 60% | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score:100%, Worst Postbaseline score:90% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:70% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score:100%, Worst Postbaseline score:100% | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 80% | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:80% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 70% | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 90% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 70% | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 60%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:60% | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 40% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 60% | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score:100% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score:100% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score:100%, Worst Postbaseline score:100% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 40% | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 80% | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 50% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 80% | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 60%, Worst Postbaseline score: 60% | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 90% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 80% | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:70% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score:100%, Worst Postbaseline score:90% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:60% | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 60% | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:80% | 1 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:80% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 90% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score:100%, Worst Postbaseline score:100% | 1 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 50% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 60%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 40% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:60% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score:100% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score:100%, Worst Postbaseline score:90% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:70% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:80% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:70% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 50% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 80% | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 90% | 4 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 60%, Worst Postbaseline score: 60% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 60% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 70% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score:100% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score:100%, Worst Postbaseline score:90% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 60% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:60% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 70% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 80% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score:100%, Worst Postbaseline score:100% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 40% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 50% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 90% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 80% | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 60% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score:100%, Worst Postbaseline score:90% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:80% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:70% | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score:100%, Worst Postbaseline score:100% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score:100% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 60%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 40% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:60% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 70% | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 60%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:60% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 90% | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:70% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 70% | 3 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:80% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 80% | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 40% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 50% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score:100%, Worst Postbaseline score:100% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score:100%, Worst Postbaseline score:90% | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score:100% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 90% | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:60% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 40% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 50% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:70% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 60%, Worst Postbaseline score: 60% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 80% | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score:100% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 80%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 90%, Worst Postbaseline score: 70% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score:100%, Worst Postbaseline score:100% | 5 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 100%, Worst Postbaseline score:80% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score: 70%, Worst Postbaseline score: 80% | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Shift From Baseline to Worst Post Baseline Score in Lansky Performance Play Score | Baseline score:100%, Worst Postbaseline score:90% | 0 Participants |
Secondary
Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Number of participants with TEAEs (serious and non-serious adverse events) and SAEs were reported based on their safety assessments of hematology, clinical chemistry, proximal tibial growth, fecal occult blood, physical examinations, regular measurement of vital signs and electrocardiogram parameter values.
Time frame: From the date of first dose of study drug up to 30 days after the last dose (up to approximately 7 years)
Population: Safety analysis set included all participants who received any study drug and had at least one post-baseline safety evaluation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 5 Participants |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 3 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 11 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 7 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 7 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 5 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 1 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 29 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 21 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 11 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 7 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 9 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 11 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 20 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 16 Participants |
Secondary
Cohorts 1, 2A, 2B, 3A and 3B: Overall Survival (OS)
OS was defined as the time from the date of the first dose of study drug until the date of death from any cause. Participants who are lost to follow-up and those who are alive at the date of data cutoff were censored at the date the participant was last known to be alive (or the data cutoff date). 95% CI of median were calculated according to Brookmeyer and Crowley method.
Time frame: From first dose of study drug until death (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
Population: Full analysis set included all enrolled participants who did not fail study screening.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Overall Survival (OS) | 8.1 months |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Overall Survival (OS) | 7.4 months |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Overall Survival (OS) | 7.7 months |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Overall Survival (OS) | 6.1 months |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Overall Survival (OS) | 10.0 months |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Overall Survival (OS) | 13.6 months |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Overall Survival (OS) | NA months |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Overall Survival (OS) | NA months |
Secondary
Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib
Duration of each cycle for Cohorts 1, 2A, 2B is 28 days. Duration of each cycle for Cohorts 3A, 3B is 21 days.
Time frame: Cohorts 1, 2A, 2B: Cycle(C)1 Day(D)1: 0.5-4 hours (h), 6-10 h post-dose, C1D15: pre-dose, 0.5-4 h, 6-10 h post-dose, C2D1: pre-dose, 2-12 h post-dose; Cohorts 3A, 3B: C1D1: 0.5-4 h, 6-10 h post-dose, C2D1: pre-dose, 2-12 h post-dose
Population: Pharmacokinetic (PK) Analysis Set included all participants who had received any study drug and had evaluable PK data. Here number analyzed, n signifies participants who were evaluable for this outcome measure at given time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 2 Day 1: 2-12 hours | 502.4 nanogram per milliliter (ng/mL) | Standard Deviation 360.71 |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 1: 6-10 hours | 212.7 nanogram per milliliter (ng/mL) | Standard Deviation 185.98 |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 15: Pre-dose | 46.9 nanogram per milliliter (ng/mL) | Standard Deviation 11.01 |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 1: 0.5-4 hours | 295.6 nanogram per milliliter (ng/mL) | Standard Deviation 214.01 |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 15: 6-10 hours | 351.8 nanogram per milliliter (ng/mL) | Standard Deviation 157.15 |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 2 Day 1: Pre-dose | 58.1 nanogram per milliliter (ng/mL) | Standard Deviation 19.58 |
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 15: 0.5-4 hours | 133.4 nanogram per milliliter (ng/mL) | Standard Deviation 163.37 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 15: 6-10 hours | 375.8 nanogram per milliliter (ng/mL) | Standard Deviation 121.21 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 1: 0.5-4 hours | 134.8 nanogram per milliliter (ng/mL) | Standard Deviation 145.83 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 2 Day 1: 2-12 hours | 440.7 nanogram per milliliter (ng/mL) | Standard Deviation 229.29 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 2 Day 1: Pre-dose | 61.6 nanogram per milliliter (ng/mL) | Standard Deviation 60.61 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 15: Pre-dose | 59.1 nanogram per milliliter (ng/mL) | Standard Deviation 29.19 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 1: 6-10 hours | 281.9 nanogram per milliliter (ng/mL) | Standard Deviation 137.39 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 15: 0.5-4 hours | 226.6 nanogram per milliliter (ng/mL) | Standard Deviation 204.61 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 1: 6-10 hours | 238.0 nanogram per milliliter (ng/mL) | Standard Deviation 135.87 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 1: 0.5-4 hours | 52.5 nanogram per milliliter (ng/mL) | Standard Deviation 81.4 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 15: Pre-dose | 96.9 nanogram per milliliter (ng/mL) | Standard Deviation 66.1 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 15: 0.5-4 hours | 191.8 nanogram per milliliter (ng/mL) | Standard Deviation 190.22 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 15: 6-10 hours | 413.0 nanogram per milliliter (ng/mL) | Standard Deviation 221.47 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 2 Day 1: Pre-dose | 97.9 nanogram per milliliter (ng/mL) | Standard Deviation 77.08 |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 2 Day 1: 2-12 hours | 339.2 nanogram per milliliter (ng/mL) | Standard Deviation 212.44 |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 2 Day 1: 2-12 hours | 102 nanogram per milliliter (ng/mL) | — |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 15: 6-10 hours | 247 nanogram per milliliter (ng/mL) | — |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 15: 0.5-4 hours | 124 nanogram per milliliter (ng/mL) | — |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 1: 0.5-4 hours | 11.1 nanogram per milliliter (ng/mL) | — |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 2 Day 1: Pre-dose | 59.8 nanogram per milliliter (ng/mL) | — |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 1: 6-10 hours | 188 nanogram per milliliter (ng/mL) | — |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 15: Pre-dose | 56.2 nanogram per milliliter (ng/mL) | — |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 15: Pre-dose | 67.0 nanogram per milliliter (ng/mL) | Standard Deviation 53.78 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 1: 6-10 hours | 289.4 nanogram per milliliter (ng/mL) | Standard Deviation 200.09 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 2 Day 1: 2-12 hours | 382.4 nanogram per milliliter (ng/mL) | Standard Deviation 217.49 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 15: 0.5-4 hours | 168.3 nanogram per milliliter (ng/mL) | Standard Deviation 157.67 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 15: 6-10 hours | 322.9 nanogram per milliliter (ng/mL) | Standard Deviation 138.87 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 2 Day 1: Pre-dose | 66.8 nanogram per milliliter (ng/mL) | Standard Deviation 62.5 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 1: 0.5-4 hours | 177.4 nanogram per milliliter (ng/mL) | Standard Deviation 191.03 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 2 Day 1: Pre-dose | 51.7 nanogram per milliliter (ng/mL) | Standard Deviation 44.23 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 2 Day 1: 2-12 hours | 205.6 nanogram per milliliter (ng/mL) | Standard Deviation 134.66 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 1: 0.5-4 hours | 105.2 nanogram per milliliter (ng/mL) | Standard Deviation 131.54 |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 1: 6-10 hours | 191.9 nanogram per milliliter (ng/mL) | Standard Deviation 100.69 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 1: 6-10 hours | 148.5 nanogram per milliliter (ng/mL) | Standard Deviation 122.41 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 1: 0.5-4 hours | 111.4 nanogram per milliliter (ng/mL) | Standard Deviation 131.47 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 2 Day 1: 2-12 hours | 237.4 nanogram per milliliter (ng/mL) | Standard Deviation 124.82 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 2 Day 1: Pre-dose | 76.1 nanogram per milliliter (ng/mL) | Standard Deviation 63.25 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 2 Day 1: 2-12 hours | 275.3 nanogram per milliliter (ng/mL) | Standard Deviation 135.73 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 2 Day 1: Pre-dose | 50.4 nanogram per milliliter (ng/mL) | Standard Deviation 65.1 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 1: 0.5-4 hours | 209.7 nanogram per milliliter (ng/mL) | Standard Deviation 197.66 |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A, and 3B: Plasma Concentrations of Lenvatinib | Cycle 1 Day 1: 6-10 hours | 164.8 nanogram per milliliter (ng/mL) | Standard Deviation 73.59 |
Secondary
Cohorts 1, 2A, 2B, 3A and 3B: Progression-free Survival (PFS)
PFS was defined as the time (in months) from the date of first dose of study drug to the date of first documentation of PD or date of death, whichever occurred first, based on RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the baseline SOD of target lesions. 95% CI of median were calculated according to Brookmeyer and Crowley method.
Time frame: From first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
Population: Full analysis set included all enrolled participants who did not fail study screening.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Progression-free Survival (PFS) | 3.7 months |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Progression-free Survival (PFS) | 6.3 months |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Progression-free Survival (PFS) | 5.5 months |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Progression-free Survival (PFS) | 5.5 months |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Progression-free Survival (PFS) | 3.0 months |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Progression-free Survival (PFS) | 7.1 months |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Progression-free Survival (PFS) | 12.0 months |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Progression-free Survival (PFS) | 6.9 months |
Secondary
Cohorts 1, 2A, 2B, 3A and 3B: Time to Progression (TTP)
TTP was defined as the time from the date of first dose of study drug to the date of first documentation of PD based on RECIST 1.1. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the baseline SOD of target lesions. 95% CI of median were calculated according to Brookmeyer and Crowley method.
Time frame: From first dose of study drug until PD (Cohort 1, Cohort 2A, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
Population: Full analysis set included all enrolled participants who did not fail study screening.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: All Participants | Cohorts 1, 2A, 2B, 3A and 3B: Time to Progression (TTP) | 3.7 months |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Time to Progression (TTP) | 6.3 months |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Time to Progression (TTP) | 5.5 months |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Time to Progression (TTP) | 5.5 months |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Time to Progression (TTP) | 3.0 months |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Time to Progression (TTP) | 7.1 months |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Time to Progression (TTP) | 12.0 months |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2A, 2B, 3A and 3B: Time to Progression (TTP) | 6.9 months |
Secondary
Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR)
BOR: best response of CR or PR for \>4 weeks or SD for \>=7 weeks from first dose, recorded from start of treatment until PD or death, whichever occurred first based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have reduction in their short axis \<10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD. PD was defined as: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Not evaluable (NE) means BOR of NE or SD of \<7 weeks duration. Unknown means no data were available on the case report form.
Time frame: From date of first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
Population: Full analysis set included all enrolled participants who did not fail study screening. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: All Participants | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Stable Disease | 2 Participants |
| Cohort 1: All Participants | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Complete Response | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Not Evaluable or Unknown | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Partial Response | 0 Participants |
| Cohort 1: All Participants | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Progressive Disease | 1 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Stable Disease | 5 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Partial Response | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Progressive Disease | 2 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Complete Response | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Not Evaluable or Unknown | 2 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Not Evaluable or Unknown | 2 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Partial Response | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Complete Response | 0 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Stable Disease | 4 Participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Progressive Disease | 4 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Stable Disease | 13 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Complete Response | 0 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Partial Response | 2 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Progressive Disease | 12 Participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Not Evaluable or Unknown | 3 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Complete Response | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Not Evaluable or Unknown | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Stable Disease | 3 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Progressive Disease | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Partial Response | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Complete Response | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Not Evaluable or Unknown | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Progressive Disease | 2 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Partial Response | 0 Participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Stable Disease | 10 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Progressive Disease | 4 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Partial Response | 3 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Stable Disease | 9 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Complete Response | 0 Participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Number of Participants With Best Overall Response (BOR) | Not Evaluable or Unknown | 2 Participants |
Secondary
Cohorts 1, 2B, 3A, and 3B: Objective Response Rate (ORR)
ORR was defined as the percentage of participants with a BOR of CR or PR for \>4 weeks or SD for \>=7 weeks as assessed by investigator based on RECIST v1.1, recorded from start of study treatment until PD or death whichever occurred first. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. 95% CI of the ORR were calculated according to Clopper and Pearson method.
Time frame: From date of first dose of study drug until PD or death, whichever occurred first (Cohort 1, Cohort 2B: until the data cut-off date, 31 May 2019; Cohort 3A, Cohort 3B: until the data cut-off date, 18 July 2019)
Population: Full analysis set included all enrolled participants who did not fail study screening. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: All Participants | Cohorts 1, 2B, 3A, and 3B: Objective Response Rate (ORR) | 0 percentage of participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Objective Response Rate (ORR) | 0 percentage of participants |
| Cohort 1, Single-agent Dose-finding: Lenvatinib 17 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Objective Response Rate (ORR) | 0 percentage of participants |
| Cohort2B,Single-agentExpansion,Osteosarcoma:Lenvatinib14mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Objective Response Rate (ORR) | 6.7 percentage of participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 11 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Objective Response Rate (ORR) | 28.6 percentage of participants |
| Cohort 3A, Combination Dose-finding: Lenvatinib 14 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Objective Response Rate (ORR) | 0 percentage of participants |
| Cohort 3B, Combination Expansion: Lenvatinib 14 mg/m^2 | Cohorts 1, 2B, 3A, and 3B: Objective Response Rate (ORR) | 16.7 percentage of participants |