Non-small cell lung cancer, predominantly clear cell renal cell carcinoma, endometrial carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, or melanoma (excluding uveal melanoma). MedDRA version: 20.0 Level: PT Classification code 10014733 Term: Endometrial cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck S
Conditions
Interventions
Trade Name: KISPLYX 4 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: lenvatinib
CAS Number: 417716-92-8
Current Sponsor code: E7080
Other descriptive name: lenvatinib (as mesilate)
Concent
Sponsors
Eisai Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Phase 1b: Histologically and/or cytologically confirmed metastatic selected solid tumor types that have progressed after treatment with approved therapies or for which there are no standard effective therapies available. If nivolumab or pembrolizumab is an approved therapy for the subject’s tumor type, but the subject has not been treated with it, the Investigator may enroll the subject in this study. Phase 2: Histologically and/or cytologically confirmed metastatic selected solid tumor types with 0-2 prior lines of systemic therapy (unless discussed with the sponsor). As of Amendment 03, for the non-small cell lung cancer and melanoma cohorts, subjects must have progressed on or after prior treatment with one anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. Selected tumor types of both phases: non-small cell lung cancer, predominantly clear cell renal cell carcinoma, endometrial carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, or melanoma (excluding uveal melanoma). 2. Life expectancy of 12 weeks or more 3. Phase 2: Measurable disease meeting the following criteria: - At least 1 lesion of =10 mm in the longest diameter for a non-lymph node or =15 mm in the short-axis diameter for a lymph node that is serially measurable according to irRECIST using computerized tomography/magnetic resonance imaging (CT/MRI). - Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation must show subsequent evidence of substantial size increase to be deemed a target lesion. 4. Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1. 5. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP = 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Cycle 1 Day 1. 6. Adequate renal function defined as creatinine = 1.5 × ULN or calculated creatinine clearance =40 mL/min per the Cockcroft and Gault formula with creatinine levels >1.5 × ULN. 7. Adequate bone marrow function: - Absolute neutrophil count (ANC) =1500/mm3 (=1.5 × 103/µL) - Platelets = 100,000/mm3 (=100 × 109/L) - Hemoglobin = 9.0 g/dL 8. Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) = 1.5. 9. Adequate liver function as evidenced by bilirubin =1.5 times the upper limit of normal (ULN) and alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) =3×ULN (in the case of liver metastases =5×ULN). In case ALP is >3×ULN (in the absence of liver metastases) or >5×ULN (in the presence of liver metastases) AND the subject also is known to have bone metastases, the liver specific ALP isoenzyme must be separated from the total and used to assess the liver function instead of the total ALP. 10. Males or females age = 18 years at the time of informed consent. 11. Subjects with known brain metastases will be eligible if they have completed the primary brain therapy (such as whole brain radiotherapy, stereotactic radiosurgery or complete surgical resection) and if they have remained clinically stable, asymptomatic and off of steroids for at least 28 days before starting study treatment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 13 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: 1. Prior anticancer treatment within 28 days (or 5 times the half-life, whichever is shorter) or any investigational agent within 30 days prior to the first dose of study drugs. All acute toxicities related to prior treatments must be resolved to Grade =1. 2. Subjects must have recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy. 3. Subjects having >1+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with urine protein =1 g/24-hour will be ineligible. 4. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib 5. New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months 6. Prolongation of QTc interval to >480 msec 7. Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug 8. Active infection (any infection requiring systemic treatment) 9. Subject is known to be positive for Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C 10. Serious nonhealing wound, ulcer, or bone fracture 11. Known intolerance to either of the study drugs (or any of the excipients) 12. History of organ allograft 13. Biologic response modifiers (eg, granulocyte colony-stimulating factor) within 4 weeks before study entry. Chronic erythropoietin therapy is permitted provided that no dose adjustments were made within 2 months before first dose of study treatment. 14. Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical study 15. Females who are pregnant or breastfeeding 16. Excluding the primary tumor leading to enrollment in this study, any other active malignancy (except for definitively treated melanoma in-situ, basal or squamous cellcarcinoma of the skin, or carcinoma in-situ of the bladder or cervix) within the past 24 months 17. Prior treatment with lenvatinib or any PD-1, anti-PD-L1, or anti-PD-L2 agent, excluding the melanoma, NSCLC cohorts, where prior treatment with one PD-1, anti-PD-L1, or anti-PD-L2 agent is allowed. 18. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids (up to 7.5mg/d of prednisone or equivalent) may be approved after consultation with the sponsor. 19. No active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 20. Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis 21. Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1b – Determination and confirmation of the maximum tolerated dose (MTD): To determine and confirm the MTD for lenvatinib in combination with 200 mg (IV, Q3W) pembrolizumab in subjects with selected solid tumors. Phase 2 – Expansion In Selected Tumor Types (Expansion): To evaluate objective response rate as of Week 24 (ORR(Week 24): complete response + partial response [CR(Week 24) + PR(Week 24)]) of lenvatinib in combination with pembrolizumab in each of the cohorts using immune-related RECIST (irRECIST).;Secondary Objective: To assess: - the tolerability and safety profile of lenvatinib in combination with pembrolizumab - ORR by irRECIST of lenvatinib in combination with pembrolizumab in subjects with solid tumors - Progression-free survival (PFS) by irRECIST - Overall survival (OS) - Duration of response (DOR) by irRECIST - Disease control rate (DCR: CR + PR + stable disease [SD]) by irRECIST - Durable Stable Disease rate (DSDR (SD =23 weeks)) by irRECIST - Clinical benefit rate (CBR: CR, PR + durable SD) by irRECIST - Pharmacokinetic (PK) profiles of lenvatinib during combination treatment.;Primary end point(s): ORR(Week 24) is defined as the proportion of subjects who have BOR of irCR(Week 24) or irPR(Week 24) as of the Week 24 tumor assessment time point.;Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ORR is defined as the proportion of subjects who have BOR of irCR or irPR at the time of data cutoff. PFS is defined as the time from the first study dose date to the date of first documentation of confirmed disease progression or death (whichever occurs first). OS is measured from the start date of the treatment period until date of death from any cause. Subjects who are lost to follow-up and the subjects who are alive at the date of data cutoff will be censored at the date the subject was last known alive. DCR is defined as the proportion of subjects who have BOR of irCR or irPR or irSD (minimum duration from C1D1 to irSD =5 weeks). CBR is defined as the proportion of subjects who have BOR of irCR or irPR or durable irSD (duration of irSD =23 weeks). DOR is defined as the duration of irCR or irPR. Durable SD rate is defined as the proportion of subjects whose BOR is irSD and the duration of irSD =23weeks.;Timepoint(s) of evaluation of this end point: ORR: at the time of data cutoff. PFS: the date of first documentation of confirmed disease progression or death (whichever occurs first). OS: date of death from any cause. Subjects who are lost to follow-up and the subjects who are alive at the date of data cutoff will be censored at the date the subject was last known alive. DCR (minimum duration from C1D1 to irSD =5 weeks). CBR (duration of irSD =23 weeks). DOR is defined as the duration of irCR or irPR. Durable SD rate: duration of irSD =23weeks. | — |
Countries
Spain, United States
Contacts
Public ContactGlobal Regulatory Strategy
Eisai Ltd.
Outcome results
None listed