Advanced and Metastatic Cancer Patients With Tumors Harboring FGF/FGFR Tumors, Breast Cancer, Cholangiocarcinoma, Gastric Cancer, Primary CNS Tumors, Urothelial Cancer
Conditions
Keywords
FGF, FGFR, Futibatinib, TAS-120
Brief summary
This is an open-label, nonrandomized, Phase 1/2 study for the fibroblast growth factor receptor (FGFR) inhibitor futibatinib (TAS-120). The purpose of the study is to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic, and anti-tumor activity of futibatinib in patients with advanced solid tumors with and without genomic FGF/FGFR abnormalities. The study will be conducted in 3 parts: 1. Dose escalation portion to determine the -Maximum Tolerated Dose and/ or Recommended Phase 2 Dose of futibatinib. 2. Phase 1 expansion portion to further evaluate the safety and efficacy of futibatinib in patients with tumors harboring FGF/FGFR aberrations, including patients with cholangiocarcinoma (CCA), primary central nervous system tumors, urothelial carcinoma, breast cancer, gastric cancer. 3. Phase 2 study portion to confirm objective response rate of futibatinib in intrahepatic CCA patients with tumors harboring FGFR2 gene rearrangements (incl fusions).
Interventions
DRUGFutibatinib
oral once daily dosing, 21-day cycle
Sponsors
Taiho Oncology, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Provide written informed consent 2. Age ≥ 18 years of age 3. Has histologically or cytologically confirmed, locally advanced or metastatic cancer 4. The following specific criteria for each study portion Phase 1 (Dose Escalation): * Patients with any type of solid tumor * Disease progression following standard therapies or intolerant to prior standard therapies Phase 1 (Dose Expansion) * Have at least one FGF/FGFR aberration * Disease progression following standard therapies or were intolerant to prior standard therapies (including prior FGFR inhibitors). * Have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009) for advanced solid tumors or Response Assessment in Neuro-Oncology criteria (2010) for brain tumors. * Patients with any of the following tumor types * Patients with intrahepatic or extrahepatic CCA harboring FGFR2 gene fusions or other FGFR2 aberrations * Patients with primary CNS tumors * Patients with advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations * Patients with breast cancer or gastric cancer * Patients with other solid tumor types harboring FGFR gene fusions or activating mutations * Patients with solid tumor types and other FGF/FGFR alterations not listed above Phase 2 * Patients with iCCA and FGFR2 gene rearrangements (incl fusions) * Have been treated with at least one prior systemic gemcitabine and platinum-based chemotherapy * Must have documentation of radiographic progression of disease * No prior FGFR inhibitor * Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009) 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 6. Adequate organ function.
Exclusion criteria
1. History and/or current evidence of clinically significant non-tumor related alteration of calcium-phosphorus homeostasis. 2. History and/or current evidence of clinically significant ectopic mineralization/calcification. 3. History and/or current evidence of clinically significant retinal disorder 4. A serious illness or medical condition(s) 5. Pregnant or breast-feeding female
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Dose Escalation-Maximum Tolerated Dose (MTD) | Cycle 1 (21-day cycle) | MTD:Highest dose level at which \<33% of participants experience dose-limiting toxicity (DLT) during Cycle1. DLT: \>=Grade(G)3: - nonhematologic toxicity, - nausea/vomiting lasting \>48hrs(uncontrolled by aggressive antiemetic), - diarrhea lasting \>48hrs (unresponsive to antidiarrheal drug); G4 neutropenia lasting \>7days; Febrile neutropenia (ANC\<1000/mm\^3 with body temperature=\>38.3°C/sustained temperature \>=38°C for \>1hr; Thrombocytopenia G4/G3 with bleeding, required blood transfusion; Corneal disorder worsened by 1 grade or more; Increased phosphorus: \>=9mg/dL or \>=7mg/dL lasting for \>=7days or phosphate lowering therapy\[PLT\] for 7days); Creatinine increase (\>1.5×upper limit of normal \[ULN\]) lasting for \>=7 days associated with serum phosphorus \>5.5 mg/dL(PLT=7days)/calcium×phosphorus \>55 mg/dL(PLT=7days); Hypercalcemia G2 for \>7days or G3; Ectopic de novo calcification in soft tissues; \>G2 DLT: prevented Cycle 1 completion, inability to start Cycle 2 within 2 weeks of schedule. |
| Phase 1: Dose Escalation-Recommended Phase 2 Dose (RP2D) of TAS-120 | Cycle 1 (21-day cycle) | RP2D was MTD or less. MTD: Highest dose level at which \<33% of participants experience DLT) during Cycle1. DLT: \>=Grade(G)3: - nonhematologic toxicity, - nausea/vomiting lasting \>48hrs(uncontrolled by aggressive antiemetic), - diarrhea lasting \>48hrs (unresponsive to antidiarrheal drug); G4 neutropenia lasting \>7days; Febrile neutropenia (ANC\<1000/mm\^3 with body temperature=\>38.3°C/sustained temperature \>=38°C for \>1hr; Thrombocytopenia G4/G3 with bleeding, required blood transfusion; Corneal disorder worsened by 1 grade or more; Increased phosphorus: \>=9mg/dL or \>=7mg/dL lasting for \>=7days or phosphate lowering therapy\[PLT\] for 7days); Creatinine increase (\>1.5×upper limit of normal \[ULN\]) lasting for \>=7 days associated with serum phosphorus \>5.5 mg/dL(PLT=7days)/calcium×phosphorus \>55 mg/dL(PLT=7days); Hypercalcemia G2 for \>7days or G3; Ectopic de novo calcification in soft tissues; \>G2 DLT: prevented Cycle 1 completion, inability to start Cycle 2 within 2 weeks of schedule. |
| Phase 1: Dose Expansion: Percentage of Participants With Objective Response | Up to approximately 50.5 months (through cut-off date 29-May-2021) for Cohorts 1 to 6; up to approximately 27.5 months (through cut-off date 30-Jun-2019) for pooled sub-cohorts | Objective response was defined as proportion of participants who had achieved best overall response of partial response (PR) or complete response (CR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The CR was defined as a disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must had reduction in short axis to \<10 millimeters (mm) and PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions. For Cohorts 1 to 6: Objective response was based on Independent Review Committee (IRC) and for pooled Sub-cohort: Objective response was based on investigator review. |
| Phase 2: Percentage of Participants With Objective Response | Up to approximately 37.5 months (through cut-off date 29-May-2021) | Objective response was defined as proportion of participants who had achieved best overall response of PR or CR per RECIST v1.1. CR was defined as a disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must had reduction in short axis to \<10 mm and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. The Phase 2 evaluation of objective response was based on central independent CT/MRI image assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Dose Expansion: Progression-free Survival (PFS) | up to approximately 27.5 months (through cut-off date 30-Jun-2019) | A PFS was defined as the time (in months) from the day of the first dose to the date of first documented disease progression or death (due to any cause), whichever occurred first. Participants who died without a reported disease progression were considered to have progressed on the date of their death, participants who did not progress or die were censored on the date of their last tumor assessment, participants who had no on-study assessments and did not die were censored on the first dosing date, and participants who started any subsequent anti-cancer therapy without a prior reported progression were censored at the last tumor assessment prior to initiation of the subsequent anti-cancer therapy. PFS assessment per protocol was by IRC assessment for Cohorts 1 to 6 and for pooled Sub-cohort: PFS was based on investigator review. |
| Phase 2: Progression-free Survival (PFS) | Up to approximately 37.5 months (through cut-off date 29-May-2021) | A PFS was defined as the time (in months) from the day of the first dose to the date of first objectively documented disease progression or death (any cause), whichever occurred first. Participants who had died without a reported disease progression were considered to have progressed on the date of their death, participants who did not progress or die were censored on the date of their last tumor assessment, participants who had no on-study assessments and did not die were censored on the first dosing date, and participants who started any subsequent anti-cancer therapy without a prior reported progression were censored at the last tumor assessment prior to initiation of the subsequent anti-cancer therapy. PFS was analyzed as using Kaplan-Meier estimate. |
| Phase 1: Dose Expansion: Overall Survival (OS) | up to approximately 27.5 months (through cut-off date 30-Jun-2019) | An OS was defined as the time (in months) from the date of the first dose to the death date. In the absence of death confirmation or for participants alive as of the OS cut-off date, survival time was censored at the date of last study follow-up, or the cut-off date, whichever was earlier. |
| Phase 2: Overall Survival (OS) | Up to approximately 37.5 months (through cut-off date 29-May-2021) | An OS was defined as the time (in months) from the date of the first dose to the death date. In the absence of death confirmation or for participants alive as of the OS cut-off date, survival time was censored at the date of last study follow-up, or the cut-off date, whichever was earlier. |
| Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months]) | EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category. |
| Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months]) | EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category. |
| Phase 1: Dose Expansion: Duration of Response (DOR) | Up to approximately 50.5 months (through cut-off date 29-May-2021) for Cohorts 1 to 6; up to approximately 27.5 months (through cut-off date 30-Jun-2019) for pooled sub-cohorts | A DOR was defined as the time (in months) from the first documentation of response (CR or PR) to the first documentation of objective progressive disease (PD) or death due to any cause, whichever occurred first. Participants who started subsequent anticancer therapy without a prior reported progression were censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy. For Cohorts 1 to 6: DOR was based on IRC and for Group 3, 4, 5, 6 and for pooled Sub-cohort: DOR was based on investigator review. |
| Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months]) | EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category. |
| Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months]) | EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category. |
| Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits | Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months]) | EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. A vertical VAS allows the participants to indicate their health state that day, and ranged from 0 (worst imaginable) to 100 (best imaginable), with higher scores indicating better health state. |
| Phase 2:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints | Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months]) | EORTC QLQ-C30 is a cancer-specific instrument that contains 30 questions for evaluation of new chemotherapy & assessment of participant reported outcome. EORTC QLQ-C30 included global health status/quality of life (GHS/QOL), functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), and 6 single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most questions from QLQ-C30 are 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale & are 7-point scale (1/Very Poor to 7/Excellent). GHS total score is calculated as (\[{Q29+Q30}/2\]-1)/6\*100. Answers are converted into grading scale, with values between 0 (worse outcome) to100 (best outcome). High score represents a favorable outcome with best quality of life for participant. |
| Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs) | From the first dose up to approximately 50.5 months (through cut-off date 29-May-2021) | An AE was defined as any untoward medical condition that occurred in a participant from the time the informed consent form (ICF) was signed and does not necessarily had a causal relationship with the use of the product. An SAE was an AE that falls into one or more of the following categories: a. resulted in death, b. was life threatening, c. required inpatient hospitalization or prolongation of existing hospitalization, d. resulted in persistent or significant disability or incapacity, e. was a congenital anomaly/birth defect, f. other important medical event. |
| Phase 2: Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) | From the first dose up to approximately 37.5 months (through cut-off date 29-May-2021) | An AE was defined as any untoward medical condition that occurs in a participant from the time the informed consent form (ICF) was signed and does not necessarily had a causal relationship with the use of the product. An SAE was an AE that falls into one or more of the following categories: a. resulted in death, b. was life threatening, c. required inpatient hospitalization or prolongation of existing hospitalization, d. resulted in persistent or significant disability or incapacity, e. was a congenital anomaly/birth defect, f. other important medical event. |
| Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months]) | EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category. |
| Phase 2: Duration of Response (DOR) | Up to approximately 37.5 months (through cut-off date 29-May-2021) | A DOR was defined as the time (in months) from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. Participants who started subsequent anticancer therapy without a prior reported progression were censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy. Kaplan-Meier method was used for the analysis. |
| Phase 1: Dose Expansion: Disease Control Rate (DCR) | Up to approximately 50.5 months (through cut-off date 29-May-2021) for Cohorts 1 to 6; up to approximately 27.5 months (through cut-off date 30-Jun-2019) for pooled sub-cohort | A DCR was defined as the proportion of participants with objective evidence of CR, PR, or stable disease (SD), except that there was no requirement for a confirmation of an SD, if it is maintained for at least 6 weeks post treatment initiation. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes might had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the Baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taken as a reference the smallest sum diameters while on study. For Cohorts 1 to 6: DCR was based on IRC and for pooled Sub-cohort: DCR was based on investigator review. |
| Phase 2: Disease Control Rate (DCR) | Up to approximately 37.5 months (through cut-off date 29-May-2021) | A DCR was defined as the proportion of participants with objective evidence of CR, PR, or SD, except that there was no requirement for a confirmation of an SD response, if it is maintained for at least 6 weeks post treatment initiation. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes might had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the Baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taken as a reference the smallest sum diameters while on study. DCR was based on IRC. |
Countries
Australia, Canada, France, Germany, Hong Kong, Italy, Japan, Netherlands, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Study had Phase 1 and 2. Phase 1 included Dose escalation: 86 participants were enrolled & treated and Dose Expansion: 284 participants were screened, of which 201 were enrolled; 197 were treated & 4 were not treated. Phase 2: 120 participants signed informed consent, of which 17 were screen failures & thus 103 were treated. In Participant Flow, Baseline Characteristics & Adverse events, combined arm presentation of QOD & QD dosing was made for Phase 1 Dose Escalation as pre-planned in protocol.
Pre-assignment details
All Phase 1 Dose Expansion (DE) sub-cohort 1 and 2 participants: efficacy data were presented only per cut-off date (COD) 30-Jun-2019 because they had disease progression & discontinued & thus not available for COD 29-May-2021 analysis. For Phase 1 DE, primary analysis (progression free survival and overall survival) data were presented per COD 30-Jun-2019 as pre planned in protocol. Phase 1 and 2 participants who showed clinical benefit: efficacy data were presented per COD 29-May-2021.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: Dose Escalation: QOD Dosing: 8 mg Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 8 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 6 |
| Phase 1: Dose Escalation: QOD Dosing: 16 mg Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 16 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 3 |
| Phase 1: Dose Escalation: QOD Dosing: 24 mg Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 24 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 3 |
| Phase 1: Dose Escalation: QOD Dosing: 36 mg Participants with or without FGF/FGFR gene abnormalities received orally TAS-120 36 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 3 |
| Phase 1: Dose Escalation: QOD Dosing: 56 mg Participants with FGF/FGFR gene abnormalities received orally TAS-120 56 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 3 |
| Phase 1: Dose Escalation: QOD Dosing: 80 mg Participants with FGF/FGFR gene abnormalities received orally TAS-120 80 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 5 |
| Phase 1: Dose Escalation: QOD Dosing: 120 mg Participants with FGF/FGFR gene abnormalities received orally TAS-120 120 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 4 |
| Phase 1: Dose Escalation: QOD Dosing: 160 mg Participants with FGF/FGFR gene abnormalities received orally TAS-120 160 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 8 |
| Phase 1: Dose Escalation: QOD Dosing: 200 mg Participants with FGF/FGFR gene abnormalities received orally TAS-120 200 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 7 |
| Phase 1: Dose Escalation: QD Dosing: 4 mg Participants with or without FGF/FGFR gene abnormalities received a dose between 4 mg orally once daily (QD) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 4 |
| Phase 1: Dose Escalation: QD Dosing: 8 mg Participants with or without FGF/FGFR gene abnormalities received a dose between 8 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 5 |
| Phase 1: Dose Escalation: QD Dosing: 16 mg Participants with or without FGF/FGFR gene abnormalities received a dose between 16 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 14 |
| Phase 1: Dose Escalation: QD Dosing: 20 mg Participants with or without FGF/FGFR gene abnormalities received a dose between 20 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 7 |
| Phase 1: Dose Escalation: QD Dosing: 24 mg Participants with or without FGF/FGFR gene abnormalities received a dose between 24 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 14 |
| Phase 1: Dose Expansion Cohort 1 Participants with intra-hepatic or extrahepatic cholangiocarcinoma (iCCA or eCCA) harboring FGFR2 gene fusions or rearrangements and who were treated or not treated with prior FGFR inhibitors received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 57 |
| Phase 1: Dose Expansion: Cohort 2 Participants with primary central nervous system (CNS) tumors harboring FGFR gene fusions or FGFR1 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 34 |
| Phase 1: Dose Expansion: Cohort 3 Participants with advanced urothelial carcinoma harboring FGFR3 gene fusions or FGFR3 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 15 |
| Phase 1: Dose Expansion: Cohort 4 Participants with breast or gastric cancer with harboring FGFR2 amplification received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 13 |
| Phase 1: Dose Expansion: Cohort 5 Participants with tumor types harboring FGFR gene fusions or activating mutations received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 24 |
| Phase 1: Dose Expansion: Cohort 6 Participants who were not included in Cohorts 1 to 5 received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 27 |
| Phase 1: Dose Expansion: Sub-cohort 1 Participants with iCCA who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 19 |
| Phase 1: Dose Expansion: Sub-cohort 2 Participants with other tumor types who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 8 |
| Phase 2 Participants with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death. | 103 |
| Total | 386 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 | FG021 | FG022 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Dose Escalation(Approximately 60 Months) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation(Approximately 60 Months) | Clinical disease progression | 2 | 1 | 1 | 2 | 1 | 1 | 3 | 2 | 1 | 0 | 0 | 2 | 2 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation(Approximately 60 Months) | Death | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation(Approximately 60 Months) | Investigator decision | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation(Approximately 60 Months) | Radiographic progression | 4 | 2 | 2 | 1 | 2 | 3 | 0 | 6 | 5 | 4 | 5 | 11 | 4 | 7 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation(Approximately 60 Months) | Withdrawal by participant | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Expansion (Approximately 59 Months) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 1 | 3 | 0 | 3 | 1 | 0 | 0 | 0 |
| Dose Expansion (Approximately 59 Months) | Clinical Disease Progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 3 | 0 | 2 | 3 | 4 | 5 | 1 | 0 |
| Dose Expansion (Approximately 59 Months) | Investigator decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 3 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Dose Expansion (Approximately 59 Months) | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 |
| Dose Expansion (Approximately 59 Months) | Radiographic progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 38 | 23 | 12 | 11 | 17 | 21 | 14 | 6 | 0 |
| Dose Expansion (Approximately 59 Months) | Untreated | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Dose Expansion (Approximately 59 Months) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Phase 2 (Approximately 63 Months) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 7 |
| Phase 2 (Approximately 63 Months) | Clinical Disease Progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 |
| Phase 2 (Approximately 63 Months) | Investigator Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Phase 2 (Approximately 63 Months) | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 7 |
| Phase 2 (Approximately 63 Months) | Radiologic Progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 78 |
| Phase 2 (Approximately 63 Months) | Untreated | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 17 |
| Phase 2 (Approximately 63 Months) | Withdrawal by participant | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Phase 1: Dose Escalation: QOD Dosing: 16 mg | Phase 1: Dose Escalation: QOD Dosing: 24 mg | Phase 1: Dose Escalation: QOD Dosing: 36 mg | Phase 1: Dose Escalation: QOD Dosing: 56 mg | Phase 1: Dose Escalation: QOD Dosing: 80 mg | Phase 1: Dose Escalation: QOD Dosing: 120 mg | Phase 1: Dose Escalation: QOD Dosing: 160 mg | Phase 1: Dose Escalation: QOD Dosing: 200 mg | Phase 1: Dose Escalation: QD Dosing: 4 mg | Phase 1: Dose Escalation: QD Dosing: 8 mg | Phase 1: Dose Escalation: QD Dosing: 16 mg | Phase 1: Dose Escalation: QD Dosing: 20 mg | Phase 1: Dose Escalation: QOD Dosing: 8 mg | Phase 1: Dose Escalation: QD Dosing: 24 mg | Phase 1: Dose Expansion Cohort 1 | Phase 1: Dose Expansion: Cohort 2 | Phase 1: Dose Expansion: Cohort 3 | Phase 1: Dose Expansion: Cohort 4 | Phase 1: Dose Expansion: Cohort 5 | Phase 1: Dose Expansion: Cohort 6 | Phase 1: Dose Expansion: Sub-cohort 1 | Phase 1: Dose Expansion: Sub-cohort 2 | Phase 2 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 96 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 12 Participants | 7 Participants | 10 Participants | 3 Participants | 3 Participants | 9 Participants | 1 Participants | 2 Participants | 23 Participants |
| Age, Categorical Between 18 and 65 years | 290 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 6 Participants | 5 Participants | 3 Participants | 3 Participants | 12 Participants | 4 Participants | 4 Participants | 11 Participants | 45 Participants | 27 Participants | 5 Participants | 10 Participants | 21 Participants | 18 Participants | 18 Participants | 6 Participants | 80 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 281 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 7 Participants | 6 Participants | 6 Participants | 6 Participants | 41 Participants | 19 Participants | 7 Participants | 13 Participants | 16 Participants | 23 Participants | 18 Participants | 5 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 96 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 5 Participants | 4 Participants | 2 Participants | 2 Participants | 7 Participants | 1 Participants | 0 Participants | 7 Participants | 14 Participants | 15 Participants | 8 Participants | 0 Participants | 8 Participants | 3 Participants | 0 Participants | 1 Participants | 12 Participants |
| Race/Ethnicity, Customized Asian/Oriental | 55 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 6 Participants | 2 Participants | 0 Participants | 8 Participants | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 30 Participants |
| Race/Ethnicity, Customized Black or African-American | 15 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 8 Participants |
| Race/Ethnicity, Customized Missing/Unknown | 81 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 7 Participants | 0 Participants | 0 Participants | 4 Participants | 13 Participants | 15 Participants | 8 Participants | 0 Participants | 6 Participants | 2 Participants | 1 Participants | 1 Participants | 13 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White/Caucasian | 233 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants | 3 Participants | 5 Participants | 5 Participants | 3 Participants | 4 Participants | 7 Participants | 6 Participants | 6 Participants | 8 Participants | 37 Participants | 17 Participants | 7 Participants | 2 Participants | 15 Participants | 22 Participants | 16 Participants | 7 Participants | 51 Participants |
| Sex: Female, Male Female | 226 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 4 Participants | 1 Participants | 4 Participants | 5 Participants | 2 Participants | 0 Participants | 8 Participants | 6 Participants | 4 Participants | 13 Participants | 40 Participants | 12 Participants | 4 Participants | 9 Participants | 14 Participants | 16 Participants | 14 Participants | 7 Participants | 58 Participants |
| Sex: Female, Male Male | 160 Participants | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 3 Participants | 4 Participants | 2 Participants | 2 Participants | 5 Participants | 6 Participants | 1 Participants | 2 Participants | 1 Participants | 17 Participants | 22 Participants | 11 Participants | 4 Participants | 10 Participants | 11 Participants | 5 Participants | 1 Participants | 45 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 | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 5 | 1 / 4 | 0 / 8 | 2 / 7 | 0 / 4 | 0 / 5 | 2 / 14 | 1 / 7 | 1 / 14 | 40 / 57 | 22 / 34 | 12 / 15 | 11 / 13 | 15 / 24 | 17 / 27 | 1 / 8 | 9 / 19 | 58 / 103 |
| other Total, other adverse events | 6 / 6 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 5 / 5 | 4 / 4 | 8 / 8 | 7 / 7 | 4 / 4 | 5 / 5 | 14 / 14 | 7 / 7 | 14 / 14 | 57 / 57 | 34 / 34 | 15 / 15 | 13 / 13 | 23 / 24 | 26 / 27 | 8 / 8 | 19 / 19 | 103 / 103 |
| serious Total, serious adverse events | 1 / 6 | 0 / 3 | 1 / 3 | 1 / 3 | 1 / 3 | 2 / 5 | 4 / 4 | 7 / 8 | 4 / 7 | 0 / 4 | 1 / 5 | 9 / 14 | 3 / 7 | 6 / 14 | 27 / 57 | 13 / 34 | 10 / 15 | 9 / 13 | 13 / 24 | 14 / 27 | 0 / 8 | 0 / 19 | 42 / 103 |
Outcome results
Primary
Phase 1: Dose Escalation-Maximum Tolerated Dose (MTD)
MTD:Highest dose level at which \<33% of participants experience dose-limiting toxicity (DLT) during Cycle1. DLT: \>=Grade(G)3: - nonhematologic toxicity, - nausea/vomiting lasting \>48hrs(uncontrolled by aggressive antiemetic), - diarrhea lasting \>48hrs (unresponsive to antidiarrheal drug); G4 neutropenia lasting \>7days; Febrile neutropenia (ANC\<1000/mm\^3 with body temperature=\>38.3°C/sustained temperature \>=38°C for \>1hr; Thrombocytopenia G4/G3 with bleeding, required blood transfusion; Corneal disorder worsened by 1 grade or more; Increased phosphorus: \>=9mg/dL or \>=7mg/dL lasting for \>=7days or phosphate lowering therapy\[PLT\] for 7days); Creatinine increase (\>1.5×upper limit of normal \[ULN\]) lasting for \>=7 days associated with serum phosphorus \>5.5 mg/dL(PLT=7days)/calcium×phosphorus \>55 mg/dL(PLT=7days); Hypercalcemia G2 for \>7days or G3; Ectopic de novo calcification in soft tissues; \>G2 DLT: prevented Cycle 1 completion, inability to start Cycle 2 within 2 weeks of schedule.
Time frame: Cycle 1 (21-day cycle)
Population: Analysis was performed on DLT evaluable population that included all participants in Phase 1 Dose Escalation who had either experience a DLT during the first cycle of treatment or who had complete the first cycle with at least 80% of planned TAS-120 administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 1: Dose Escalation-Maximum Tolerated Dose (MTD) | NA Milligrams |
| Phase 1: Dose Escalation: QD Dosing | Phase 1: Dose Escalation-Maximum Tolerated Dose (MTD) | 20 Milligrams |
Primary
Phase 1: Dose Escalation-Recommended Phase 2 Dose (RP2D) of TAS-120
RP2D was MTD or less. MTD: Highest dose level at which \<33% of participants experience DLT) during Cycle1. DLT: \>=Grade(G)3: - nonhematologic toxicity, - nausea/vomiting lasting \>48hrs(uncontrolled by aggressive antiemetic), - diarrhea lasting \>48hrs (unresponsive to antidiarrheal drug); G4 neutropenia lasting \>7days; Febrile neutropenia (ANC\<1000/mm\^3 with body temperature=\>38.3°C/sustained temperature \>=38°C for \>1hr; Thrombocytopenia G4/G3 with bleeding, required blood transfusion; Corneal disorder worsened by 1 grade or more; Increased phosphorus: \>=9mg/dL or \>=7mg/dL lasting for \>=7days or phosphate lowering therapy\[PLT\] for 7days); Creatinine increase (\>1.5×upper limit of normal \[ULN\]) lasting for \>=7 days associated with serum phosphorus \>5.5 mg/dL(PLT=7days)/calcium×phosphorus \>55 mg/dL(PLT=7days); Hypercalcemia G2 for \>7days or G3; Ectopic de novo calcification in soft tissues; \>G2 DLT: prevented Cycle 1 completion, inability to start Cycle 2 within 2 weeks of schedule.
Time frame: Cycle 1 (21-day cycle)
Population: Analysis was performed on DLT evaluable population that included all participants in Phase 1 Dose Escalation who had either experience a DLT during the first cycle of treatment or who had complete the first cycle with at least 80% of planned TAS-120 administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 1: Dose Escalation-Recommended Phase 2 Dose (RP2D) of TAS-120 | NA Milligrams |
| Phase 1: Dose Escalation: QD Dosing | Phase 1: Dose Escalation-Recommended Phase 2 Dose (RP2D) of TAS-120 | 20 Milligrams |
Primary
Phase 1: Dose Expansion: Percentage of Participants With Objective Response
Objective response was defined as proportion of participants who had achieved best overall response of partial response (PR) or complete response (CR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The CR was defined as a disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must had reduction in short axis to \<10 millimeters (mm) and PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions. For Cohorts 1 to 6: Objective response was based on Independent Review Committee (IRC) and for pooled Sub-cohort: Objective response was based on investigator review.
Time frame: Up to approximately 50.5 months (through cut-off date 29-May-2021) for Cohorts 1 to 6; up to approximately 27.5 months (through cut-off date 30-Jun-2019) for pooled sub-cohorts
Population: Efficacy population included all participants who had received at least 1 dose of TAS-120. Data was planned to be collected and analyzed on pooled population of participants who received 16 mg of TAS-120 in the sub-cohorts 1and 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 1: Dose Expansion: Percentage of Participants With Objective Response | 15.8 Percentage of participants |
| Phase 1: Dose Escalation: QD Dosing | Phase 1: Dose Expansion: Percentage of Participants With Objective Response | 8.8 Percentage of participants |
| Phase 1: Dose Expansion: Cohort 3 | Phase 1: Dose Expansion: Percentage of Participants With Objective Response | 13.3 Percentage of participants |
| Phase 1: Dose Expansion: Cohort 4 | Phase 1: Dose Expansion: Percentage of Participants With Objective Response | 0 Percentage of participants |
| Phase 1: Dose Expansion: Cohort 5 | Phase 1: Dose Expansion: Percentage of Participants With Objective Response | 12.5 Percentage of participants |
| Phase 1: Dose Expansion: Cohort 6 | Phase 1: Dose Expansion: Percentage of Participants With Objective Response | 0 Percentage of participants |
| Phase 1: Dose Expansion: Pooled Sub-cohort | Phase 1: Dose Expansion: Percentage of Participants With Objective Response | 33.3 Percentage of participants |
Primary
Phase 2: Percentage of Participants With Objective Response
Objective response was defined as proportion of participants who had achieved best overall response of PR or CR per RECIST v1.1. CR was defined as a disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must had reduction in short axis to \<10 mm and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. The Phase 2 evaluation of objective response was based on central independent CT/MRI image assessment.
Time frame: Up to approximately 37.5 months (through cut-off date 29-May-2021)
Population: Efficacy population included all treated iCCA participants with confirmed FGFR2 gene fusions or other FGFR2 rearrangements who had received at least 1 dose of TAS-120.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Percentage of Participants With Objective Response | 41.7 Percentage of participants |
Secondary
Phase 1: Dose Expansion: Disease Control Rate (DCR)
A DCR was defined as the proportion of participants with objective evidence of CR, PR, or stable disease (SD), except that there was no requirement for a confirmation of an SD, if it is maintained for at least 6 weeks post treatment initiation. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes might had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the Baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taken as a reference the smallest sum diameters while on study. For Cohorts 1 to 6: DCR was based on IRC and for pooled Sub-cohort: DCR was based on investigator review.
Time frame: Up to approximately 50.5 months (through cut-off date 29-May-2021) for Cohorts 1 to 6; up to approximately 27.5 months (through cut-off date 30-Jun-2019) for pooled sub-cohort
Population: Efficacy population included all participants who had received at least 1 dose of TAS-120. Data was planned to be collected and analyzed on pooled population of participants who received 16 mg of TAS-120 in the sub-cohorts 1 and 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 1: Dose Expansion: Disease Control Rate (DCR) | 66.7 Percentage of participants |
| Phase 1: Dose Escalation: QD Dosing | Phase 1: Dose Expansion: Disease Control Rate (DCR) | 23.5 Percentage of participants |
| Phase 1: Dose Expansion: Cohort 3 | Phase 1: Dose Expansion: Disease Control Rate (DCR) | 33.3 Percentage of participants |
| Phase 1: Dose Expansion: Cohort 4 | Phase 1: Dose Expansion: Disease Control Rate (DCR) | 38.5 Percentage of participants |
| Phase 1: Dose Expansion: Cohort 5 | Phase 1: Dose Expansion: Disease Control Rate (DCR) | 54.2 Percentage of participants |
| Phase 1: Dose Expansion: Cohort 6 | Phase 1: Dose Expansion: Disease Control Rate (DCR) | 22.2 Percentage of participants |
| Phase 1: Dose Expansion: Pooled Sub-cohort | Phase 1: Dose Expansion: Disease Control Rate (DCR) | 66.7 Percentage of participants |
Secondary
Phase 1: Dose Expansion: Duration of Response (DOR)
A DOR was defined as the time (in months) from the first documentation of response (CR or PR) to the first documentation of objective progressive disease (PD) or death due to any cause, whichever occurred first. Participants who started subsequent anticancer therapy without a prior reported progression were censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy. For Cohorts 1 to 6: DOR was based on IRC and for Group 3, 4, 5, 6 and for pooled Sub-cohort: DOR was based on investigator review.
Time frame: Up to approximately 50.5 months (through cut-off date 29-May-2021) for Cohorts 1 to 6; up to approximately 27.5 months (through cut-off date 30-Jun-2019) for pooled sub-cohorts
Population: Analysis was performed on the subset of participants with PR or CR in efficacy population. Here, 'overall number of participants analyzed' signifies participants with available data for this outcome measure. Data was planned to be collected and analyzed on pooled population of participants who received 16 mg of TAS-120 in the sub-cohorts 1 and 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 1: Dose Expansion: Duration of Response (DOR) | 6.18 months |
| Phase 1: Dose Escalation: QD Dosing | Phase 1: Dose Expansion: Duration of Response (DOR) | 3.52 months |
| Phase 1: Dose Expansion: Cohort 3 | Phase 1: Dose Expansion: Duration of Response (DOR) | 2.45 months |
| Phase 1: Dose Expansion: Cohort 5 | Phase 1: Dose Expansion: Duration of Response (DOR) | 2.79 months |
| Phase 1: Dose Expansion: Pooled Sub-cohort | Phase 1: Dose Expansion: Duration of Response (DOR) | 8.77 months |
Secondary
Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs)
An AE was defined as any untoward medical condition that occurred in a participant from the time the informed consent form (ICF) was signed and does not necessarily had a causal relationship with the use of the product. An SAE was an AE that falls into one or more of the following categories: a. resulted in death, b. was life threatening, c. required inpatient hospitalization or prolongation of existing hospitalization, d. resulted in persistent or significant disability or incapacity, e. was a congenital anomaly/birth defect, f. other important medical event.
Time frame: From the first dose up to approximately 50.5 months (through cut-off date 29-May-2021)
Population: Safety Population (all treated participants) included all participants who had received at least 1 dose of TAS-120.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs) | AEs | 57 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs) | SAEs | 27 Participants |
| Phase 1: Dose Escalation: QD Dosing | Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs) | AEs | 34 Participants |
| Phase 1: Dose Escalation: QD Dosing | Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs) | SAEs | 13 Participants |
| Phase 1: Dose Expansion: Cohort 3 | Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs) | AEs | 15 Participants |
| Phase 1: Dose Expansion: Cohort 3 | Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs) | SAEs | 10 Participants |
| Phase 1: Dose Expansion: Cohort 4 | Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs) | AEs | 13 Participants |
| Phase 1: Dose Expansion: Cohort 4 | Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs) | SAEs | 9 Participants |
| Phase 1: Dose Expansion: Cohort 5 | Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs) | AEs | 23 Participants |
| Phase 1: Dose Expansion: Cohort 5 | Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs) | SAEs | 13 Participants |
| Phase 1: Dose Expansion: Cohort 6 | Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs) | AEs | 26 Participants |
| Phase 1: Dose Expansion: Cohort 6 | Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs) | SAEs | 14 Participants |
| Phase 1: Dose Expansion: Pooled Sub-cohort | Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs) | SAEs | 0 Participants |
| Phase 1: Dose Expansion: Pooled Sub-cohort | Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs) | AEs | 18 Participants |
| Phase 1: Dose Expansion: Sub-cohort 2 | Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs) | AEs | 5 Participants |
| Phase 1: Dose Expansion: Sub-cohort 2 | Phase 1: Dose Expansion: Number of Participants With Any Adverse Events (AEs) and Any Serious AEs (SAEs) | SAEs | 0 Participants |
Secondary
Phase 1: Dose Expansion: Overall Survival (OS)
An OS was defined as the time (in months) from the date of the first dose to the death date. In the absence of death confirmation or for participants alive as of the OS cut-off date, survival time was censored at the date of last study follow-up, or the cut-off date, whichever was earlier.
Time frame: up to approximately 27.5 months (through cut-off date 30-Jun-2019)
Population: Efficacy population included all participants who had received at least 1 dose of TAS-120. Data was planned to be collected and analyzed on pooled population of participants who received 16 mg of TAS-120 in the sub-cohorts 1 and 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 1: Dose Expansion: Overall Survival (OS) | 11.4 months |
| Phase 1: Dose Escalation: QD Dosing | Phase 1: Dose Expansion: Overall Survival (OS) | 11.8 months |
| Phase 1: Dose Expansion: Cohort 3 | Phase 1: Dose Expansion: Overall Survival (OS) | 8.6 months |
| Phase 1: Dose Expansion: Cohort 4 | Phase 1: Dose Expansion: Overall Survival (OS) | 5.8 months |
| Phase 1: Dose Expansion: Cohort 5 | Phase 1: Dose Expansion: Overall Survival (OS) | 10.5 months |
| Phase 1: Dose Expansion: Cohort 6 | Phase 1: Dose Expansion: Overall Survival (OS) | 7.2 months |
| Phase 1: Dose Expansion: Pooled Sub-cohort | Phase 1: Dose Expansion: Overall Survival (OS) | NA months |
Secondary
Phase 1: Dose Expansion: Progression-free Survival (PFS)
A PFS was defined as the time (in months) from the day of the first dose to the date of first documented disease progression or death (due to any cause), whichever occurred first. Participants who died without a reported disease progression were considered to have progressed on the date of their death, participants who did not progress or die were censored on the date of their last tumor assessment, participants who had no on-study assessments and did not die were censored on the first dosing date, and participants who started any subsequent anti-cancer therapy without a prior reported progression were censored at the last tumor assessment prior to initiation of the subsequent anti-cancer therapy. PFS assessment per protocol was by IRC assessment for Cohorts 1 to 6 and for pooled Sub-cohort: PFS was based on investigator review.
Time frame: up to approximately 27.5 months (through cut-off date 30-Jun-2019)
Population: Efficacy population included all participants who had received at least 1 dose of TAS-120. Data was planned to be collected and analyzed on pooled population of participants who received 16 mg of TAS-120 in the sub-cohorts 1 and 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 1: Dose Expansion: Progression-free Survival (PFS) | 4.1 months |
| Phase 1: Dose Escalation: QD Dosing | Phase 1: Dose Expansion: Progression-free Survival (PFS) | 1.9 months |
| Phase 1: Dose Expansion: Cohort 3 | Phase 1: Dose Expansion: Progression-free Survival (PFS) | 1.8 months |
| Phase 1: Dose Expansion: Cohort 4 | Phase 1: Dose Expansion: Progression-free Survival (PFS) | 1.3 months |
| Phase 1: Dose Expansion: Cohort 5 | Phase 1: Dose Expansion: Progression-free Survival (PFS) | 3.5 months |
| Phase 1: Dose Expansion: Cohort 6 | Phase 1: Dose Expansion: Progression-free Survival (PFS) | 2.7 months |
| Phase 1: Dose Expansion: Pooled Sub-cohort | Phase 1: Dose Expansion: Progression-free Survival (PFS) | 6.9 months |
Secondary
Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits
EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. A vertical VAS allows the participants to indicate their health state that day, and ranged from 0 (worst imaginable) to 100 (best imaginable), with higher scores indicating better health state.
Time frame: Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
Population: Analysis was performed on PRO population. Here, 'number analyzed' = number of participants with available data for each specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits | Baseline | 71.72 score on a scale | Standard Deviation 20.307 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits | Change at Cycle 2 | -0.73 score on a scale | Standard Deviation 19.409 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits | Change at Cycle 4 | -1.04 score on a scale | Standard Deviation 23.984 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits | Change at Cycle 7 | -1.82 score on a scale | Standard Deviation 29.984 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits | Change at Cycle 10 | 0.40 score on a scale | Standard Deviation 30.428 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits | Change at Cycle 13 | 4.76 score on a scale | Standard Deviation 26.585 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits | Change at Cycle 16 | -1.71 score on a scale | Standard Deviation 34.417 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits | Change at Cycle 19 | 1.76 score on a scale | Standard Deviation 25.155 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits | Change at Cycle 22 | 1.85 score on a scale | Standard Deviation 31.707 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits | Change at Cycle 25 | -0.82 score on a scale | Standard Deviation 45.828 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits | Change at Cycle 28 | -1.85 score on a scale | Standard Deviation 40.912 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits | Change at Cycle 31 | 18.17 score on a scale | Standard Deviation 17.28 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits | Change at Cycle 34 | 19.00 score on a scale | Standard Deviation 19.313 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits | Change at Cycle 37 | 15.17 score on a scale | Standard Deviation 21.624 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits | Change at Cycle 40 | 15.00 score on a scale | — |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits | End of Treatment | -8.89 score on a scale | Standard Deviation 26.272 |
Secondary
Phase 2:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints
EORTC QLQ-C30 is a cancer-specific instrument that contains 30 questions for evaluation of new chemotherapy & assessment of participant reported outcome. EORTC QLQ-C30 included global health status/quality of life (GHS/QOL), functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), and 6 single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most questions from QLQ-C30 are 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale & are 7-point scale (1/Very Poor to 7/Excellent). GHS total score is calculated as (\[{Q29+Q30}/2\]-1)/6\*100. Answers are converted into grading scale, with values between 0 (worse outcome) to100 (best outcome). High score represents a favorable outcome with best quality of life for participant.
Time frame: Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
Population: Analysis was performed on PRO population. Here, 'number analyzed' = number of participants with available data for each specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 2:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints | Baseline | 70.1 score on scale | Standard Deviation 19.41 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints | Change at Cycle 2 | -1.0 score on scale | Standard Deviation 22.02 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints | Change at Cycle 4 | 0.4 score on scale | Standard Deviation 20.62 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints | Change at Cycle 7 | -0.5 score on scale | Standard Deviation 21.64 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints | Change at Cycle 10 | 1.9 score on scale | Standard Deviation 22.84 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints | Change at Cycle 13 | 0.9 score on scale | Standard Deviation 21.49 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints | Change at Cycle 16 | 2.5 score on scale | Standard Deviation 18.61 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints | Change at Cycle 19 | -1.7 score on scale | Standard Deviation 17.31 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints | Change at Cycle 22 | -8.3 score on scale | Standard Deviation 22.05 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints | Change at Cycle 25 | -4.8 score on scale | Standard Deviation 21.44 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints | Change at Cycle 28 | -6.3 score on scale | Standard Deviation 12.5 |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints | Change at Cycle 31 | 41.7 score on scale | — |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints | Change at Cycle 34 | 41.7 score on scale | — |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints | End of Treatment | -7.5 score on scale | Standard Deviation 23.3 |
Secondary
Phase 2: Disease Control Rate (DCR)
A DCR was defined as the proportion of participants with objective evidence of CR, PR, or SD, except that there was no requirement for a confirmation of an SD response, if it is maintained for at least 6 weeks post treatment initiation. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes might had reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the Baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taken as a reference the smallest sum diameters while on study. DCR was based on IRC.
Time frame: Up to approximately 37.5 months (through cut-off date 29-May-2021)
Population: Efficacy population included all treated iCCA participants with confirmed FGFR2 gene fusions or other FGFR2 rearrangements who had received at least 1 dose of TAS-120.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Disease Control Rate (DCR) | 82.5 Percentage of participants |
Secondary
Phase 2: Duration of Response (DOR)
A DOR was defined as the time (in months) from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. Participants who started subsequent anticancer therapy without a prior reported progression were censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy. Kaplan-Meier method was used for the analysis.
Time frame: Up to approximately 37.5 months (through cut-off date 29-May-2021)
Population: Analysis was performed on the subset of participants with PR or CR in efficacy population. Here, 'overall number of participants analyzed' signifies participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Duration of Response (DOR) | 8.31 months |
Secondary
Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits
EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category.
Time frame: Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
Population: Analysis was performed on PRO population. Here, 'number analyzed' = number of participants with available data for each specified category.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Baseline | No Problem | 64 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Baseline | Some Problem | 25 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Baseline | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 2 | No Problem | 66 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 2 | Some Problem | 15 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 2 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 4 | No Problem | 63 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 4 | Some Problem | 14 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 4 | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 7 | No Problem | 48 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 7 | Some Problem | 15 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 7 | Extreme Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 10 | No Problem | 44 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 10 | Some Problem | 12 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 10 | Extreme Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 13 | No Problem | 36 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 13 | Some Problem | 11 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 13 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 16 | No Problem | 26 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 16 | Some Problem | 8 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 16 | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 19 | No Problem | 21 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 19 | Some Problem | 6 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 19 | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 22 | No Problem | 13 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 22 | Some Problem | 8 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 22 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 25 | No Problem | 8 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 25 | Some Problem | 4 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 25 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 28 | No Problem | 5 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 28 | Some Problem | 3 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 28 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 31 | No Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 31 | Some Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 31 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 34 | No Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 34 | Some Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 34 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 37 | No Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 37 | Some Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 37 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 40 | No Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 40 | Some Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | Cycle 40 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | End of Treatment | No Problem | 22 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | End of Treatment | Some Problem | 19 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits | End of Treatment | Extreme Problem | 3 Participants |
Secondary
Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits
EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category.
Time frame: Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
Population: Patient-reported outcomes (PRO) Population that included all participants who had received TAS-120 treatment and had EQ-5D-3L assessment at Baseline and at least one subsequent post-baseline assessment. Here, 'number analyzed' = number of participants with available data for each specified category.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Baseline | No Problem | 72 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Baseline | Some Problem | 18 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Baseline | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 2 | No Problem | 60 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 2 | Some Problem | 20 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 2 | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 4 | No Problem | 60 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 4 | Some Problem | 18 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 4 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 7 | No Problem | 51 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 7 | Some Problem | 14 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 7 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 10 | No Problem | 42 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 10 | Some Problem | 16 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 10 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 13 | No Problem | 32 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 13 | Some Problem | 15 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 13 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 16 | No Problem | 23 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 16 | Some Problem | 12 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 16 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 19 | No Problem | 16 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 19 | Some Problem | 12 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 19 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 22 | No Problem | 9 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 22 | Some Problem | 12 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 22 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 25 | No Problem | 9 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 25 | Some Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 25 | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 28 | No Problem | 6 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 28 | Some Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 28 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 31 | No Problem | 3 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 31 | Some Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 31 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 34 | No Problem | 3 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 34 | Some Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 34 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 37 | No Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 37 | Some Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 37 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 40 | No Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 40 | Some Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | Cycle 40 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | End of Treatment | No Problem | 23 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | End of Treatment | Some Problem | 20 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits | End of Treatment | Extreme Problem | 1 Participants |
Secondary
Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits
EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category.
Time frame: Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
Population: Analysis was performed on PRO population. Here, 'number analyzed' = number of participants with available data for each specified category.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Baseline | No Problem | 42 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Baseline | Some Problem | 47 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Baseline | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 2 | No Problem | 45 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 2 | Some Problem | 35 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 2 | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 4 | No Problem | 40 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 4 | Some Problem | 36 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 4 | Extreme Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 7 | No Problem | 36 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 7 | Some Problem | 29 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 7 | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 10 | No Problem | 30 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 10 | Some Problem | 26 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 10 | Extreme Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 13 | No Problem | 23 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 13 | Some Problem | 22 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 13 | Extreme Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 16 | No Problem | 13 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 16 | Some Problem | 19 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 16 | Extreme Problem | 3 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 19 | No Problem | 13 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 19 | Some Problem | 15 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 19 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 22 | No Problem | 6 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 22 | Some Problem | 14 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 22 | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 25 | No Problem | 3 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 25 | Some Problem | 9 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 25 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 28 | No Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 28 | Some Problem | 5 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 28 | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 31 | No Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 31 | Some Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 31 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 34 | No Problem | 3 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 34 | Some Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 34 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 37 | No Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 37 | Some Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 37 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 40 | No Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 40 | Some Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | Cycle 40 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | End of Treatment | No Problem | 12 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | End of Treatment | Some Problem | 27 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits | End of Treatment | Extreme Problem | 5 Participants |
Secondary
Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits
EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category.
Time frame: Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
Population: Analysis was performed on PRO population. Here, 'number analyzed' = number of participants with available data for each specified category.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Baseline | No Problem | 82 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Baseline | Some Problem | 8 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Baseline | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 2 | No Problem | 75 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 2 | Some Problem | 6 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 2 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 4 | No Problem | 70 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 4 | Some Problem | 7 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 4 | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 7 | No Problem | 58 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 7 | Some Problem | 6 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 7 | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 10 | No Problem | 52 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 10 | Some Problem | 5 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 10 | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 13 | No Problem | 41 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 13 | Some Problem | 6 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 13 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 16 | No Problem | 30 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 16 | Some Problem | 4 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 16 | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 19 | No Problem | 22 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 19 | Some Problem | 6 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 19 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 22 | No Problem | 18 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 22 | Some Problem | 3 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 22 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 25 | No Problem | 9 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 25 | Some Problem | 3 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 25 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 28 | No Problem | 8 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 28 | Some Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 28 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 31 | No Problem | 3 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 31 | Some Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 31 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 34 | No Problem | 3 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 34 | Some Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 34 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 37 | No Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 37 | Some Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 37 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 40 | No Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 40 | Some Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | Cycle 40 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | End of Treatment | No Problem | 34 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | End of Treatment | Some Problem | 8 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits | End of Treatment | Extreme Problem | 1 Participants |
Secondary
Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits
EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of participants who chose each category.
Time frame: Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])
Population: Analysis was performed on PRO population. Here, 'number analyzed' = number of participants with available data for each specified category.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 13 | No Problem | 28 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 13 | Some Problem | 19 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Baseline | No Problem | 63 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Baseline | Some Problem | 24 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Baseline | Extreme Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 2 | No Problem | 47 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 2 | Some Problem | 32 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 2 | Extreme Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 4 | No Problem | 50 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 4 | Some Problem | 27 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 4 | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 7 | No Problem | 43 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 7 | Some Problem | 20 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 7 | Extreme Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 10 | No Problem | 34 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 10 | Some Problem | 23 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 10 | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 13 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 16 | No Problem | 20 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 16 | Some Problem | 14 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 16 | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 19 | No Problem | 15 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 19 | Some Problem | 12 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 19 | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 22 | No Problem | 7 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 22 | Some Problem | 14 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 22 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 25 | No Problem | 4 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 25 | Some Problem | 7 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 25 | Extreme Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 28 | No Problem | 3 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 28 | Some Problem | 5 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 28 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 31 | No Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 31 | Some Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 31 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 34 | No Problem | 2 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 34 | Some Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 34 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 37 | No Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 37 | Some Problem | 3 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 37 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 40 | No Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 40 | Some Problem | 1 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | Cycle 40 | Extreme Problem | 0 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | End of Treatment | No Problem | 16 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | End of Treatment | Some Problem | 25 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits | End of Treatment | Extreme Problem | 3 Participants |
Secondary
Phase 2: Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs)
An AE was defined as any untoward medical condition that occurs in a participant from the time the informed consent form (ICF) was signed and does not necessarily had a causal relationship with the use of the product. An SAE was an AE that falls into one or more of the following categories: a. resulted in death, b. was life threatening, c. required inpatient hospitalization or prolongation of existing hospitalization, d. resulted in persistent or significant disability or incapacity, e. was a congenital anomaly/birth defect, f. other important medical event.
Time frame: From the first dose up to approximately 37.5 months (through cut-off date 29-May-2021)
Population: Safety Population (all treated participants) included all participants who had received at least 1 dose of TAS-120.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) | AEs | 103 Participants |
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) | SAEs | 42 Participants |
Secondary
Phase 2: Overall Survival (OS)
An OS was defined as the time (in months) from the date of the first dose to the death date. In the absence of death confirmation or for participants alive as of the OS cut-off date, survival time was censored at the date of last study follow-up, or the cut-off date, whichever was earlier.
Time frame: Up to approximately 37.5 months (through cut-off date 29-May-2021)
Population: Efficacy population included all treated iCCA participants with confirmed FGFR2 gene fusions or other FGFR2 rearrangements who had received at least 1 dose of TAS-120.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Overall Survival (OS) | 20.0 months |
Secondary
Phase 2: Progression-free Survival (PFS)
A PFS was defined as the time (in months) from the day of the first dose to the date of first objectively documented disease progression or death (any cause), whichever occurred first. Participants who had died without a reported disease progression were considered to have progressed on the date of their death, participants who did not progress or die were censored on the date of their last tumor assessment, participants who had no on-study assessments and did not die were censored on the first dosing date, and participants who started any subsequent anti-cancer therapy without a prior reported progression were censored at the last tumor assessment prior to initiation of the subsequent anti-cancer therapy. PFS was analyzed as using Kaplan-Meier estimate.
Time frame: Up to approximately 37.5 months (through cut-off date 29-May-2021)
Population: Efficacy population included all treated iCCA participants with confirmed FGFR2 gene fusions or other FGFR2 rearrangements who had received at least 1 dose of TAS-120.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Dose Escalation: QOD Dosing | Phase 2: Progression-free Survival (PFS) | 8.9 months |