A Study of TAS-120 in Patients With Advanced Solid Tumors

Phase 1

Completed

Conditions: Cholangiocarcinoma
Urothelial Cancer
Advanced and Metastatic Cancer Patients With Tumors Harboring FGF/FGFR Tumors
Primary CNS Tumors
Breast Cancer
Gastric Cancer

Interventions: Drug: Futibatinib

Registration Number: NCT02052778

Lead Sponsor: Taiho Oncology, Inc.

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 407

Inclusion Criteria

Provide written informed consent
Age ≥ 18 years of age
Has histologically or cytologically confirmed, locally advanced or metastatic cancer
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)
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Adequate organ function.

Exclusion Criteria

History and/or current evidence of clinically significant non-tumor related alteration of calcium-phosphorus homeostasis.
History and/or current evidence of clinically significant ectopic mineralization/calcification.
History and/or current evidence of clinically significant retinal disorder
A serious illness or medical condition(s)
Pregnant or breast-feeding female

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1: Dose Escalation: QD Dosing: 4 mg	Futibatinib	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.
Phase 1: Dose Expansion Cohort 1	Futibatinib	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.
Phase 1: Dose Expansion: Cohort 2	Futibatinib	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.
Phase 1: Dose Expansion: Cohort 3	Futibatinib	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.
Phase 1: Dose Expansion: Cohort 4	Futibatinib	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.
Phase 1: Dose Escalation: QOD Dosing: 8 mg	Futibatinib	Participants with or without fibroblast growth factor \[FGF\]/fibroblast growth factor receptor \[FGFR\] gene abnormalities received orally TAS-120 8 milligrams (mg) orally every other day (QOD; Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.
Phase 1: Dose Escalation: QOD Dosing: 24 mg	Futibatinib	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.
Phase 1: Dose Escalation: QOD Dosing: 16 mg	Futibatinib	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.
Phase 1: Dose Escalation: QOD Dosing: 36 mg	Futibatinib	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.
Phase 1: Dose Escalation: QOD Dosing: 56 mg	Futibatinib	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.
Phase 1: Dose Escalation: QOD Dosing: 80 mg	Futibatinib	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.
Phase 1: Dose Escalation: QOD Dosing: 160 mg	Futibatinib	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.
Phase 1: Dose Escalation: QOD Dosing: 200 mg	Futibatinib	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.
Phase 1: Dose Escalation: QOD Dosing: 120 mg	Futibatinib	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.
Phase 1: Dose Escalation: QD Dosing: 8 mg	Futibatinib	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.
Phase 1: Dose Escalation: QD Dosing: 16 mg	Futibatinib	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.
Phase 1: Dose Escalation: QD Dosing: 20 mg	Futibatinib	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.
Phase 1: Dose Escalation: QD Dosing: 24 mg	Futibatinib	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.
Phase 1:Dose Expansion: Cohort 5	Futibatinib	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.
Phase 1: Dose Expansion: Cohort 6	Futibatinib	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.
Phase 1: Dose Expansion: Sub-cohort 1	Futibatinib	Participants with iCCA who were enrolled prior to the confirmation of the recommended Phase 2 dose (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.
Phase 1: Dose Expansion: Sub-cohort 2	Futibatinib	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.
Phase 2	Futibatinib	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.

Primary Outcome Measures

Name	Time	Method
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 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.
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.

Secondary Outcome Measures

Name	Time	Method
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: 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 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: 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.
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: 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 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: 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 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.

Trial Locations

Locations (58): Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
The University of Texas MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Virginia Mason Cancer Center
🇺🇸
Seattle, Washington, United States
Hospices Civils de Lyon
🇫🇷
Bron, France
UCSF Helen Diller Family Comprehensive Cancer Center. Mission Bay
🇺🇸
San Francisco, California, United States
Wayne State Universtity (Karmanos Cancer Institute)
🇺🇸
Detroit, Michigan, United States
Sunnybrook Research Institue
🇨🇦
Toronto, Canada
Banner MD Anderson Cancer Center
🇺🇸
Gilbert, Arizona, United States
Cancer Treatment Centers of America
🇺🇸
Newnan, Georgia, United States
The University of Kansas Cancer Center
🇺🇸
Fairway, Kansas, United States
Dana Farber Cancer Institution
🇺🇸
Boston, Massachusetts, United States
New Mexico Cancer Care Alliancer
🇺🇸
Albuquerque, New Mexico, United States
Spartanburg Medical Center
🇺🇸
Spartanburg, South Carolina, United States
Greenville Health System ITOR,Clinical Research Unit
🇺🇸
Greenville, South Carolina, United States
University of Pittsburgh Medical Center Hillman Cancer Center
🇺🇸
Pittsburgh, Pennsylvania, United States
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Centre Léon Bérard Bât
🇫🇷
Lyon, Cedex, France
Institut Bergonie
🇫🇷
Bordeaux, France
Pitié-Salpêtrière Hospital
🇫🇷
Paris, France
Institute Goustave-Roussy-DITEP
🇫🇷
Villejuif, France
UOC Oncologia Medica 1 I"V - Istituto Oncologico Veneto - IRCCS
🇮🇹
Padova, Italy
Hokkaido University Hospital
🇯🇵
Hokkaido, Japan
National Cancer Center Hospital
🇯🇵
Tokyo, Japan
Osaka International Cancer Institute
🇯🇵
Osaka, Japan
Seoul National University Hospital
🇰🇷
Seoul, Korea, Republic of
Val D'Hebron University Hospital
🇪🇸
Barcelona, Spain
Samsung Medical Center (Seoul)
🇰🇷
Seoul, Korea, Republic of
University Hospital Jenna
🇳🇱
Jenna, Netherlands
University Hospital Ramón y Cajal
🇪🇸
Madrid, Spain
Centro Integral Oncológico Clara Campal - Hospital Universitario Madrid Sanchinarro
🇪🇸
Madrid, Spain
Cheng Kung University Hospital
🇨🇳
Tainan, Taiwan
Sarah Cannon Research Institute
🇬🇧
London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧
Manchester, United Kingdom
University College London Hospital
🇬🇧
London, United Kingdom
University Hospital Essen, West German Cancer Center, Department of Medical Oncology
🇩🇪
Essen, Germany
Mayo Clinic (MN)
🇺🇸
Rochester, Minnesota, United States
Yonsei University, Severance Hospital (Seoul)
🇰🇷
Seoul, Korea, Republic of
ASAN Medical Center (Seoul)
🇰🇷
Seoul, Korea, Republic of
University of Utah, Huntsman Cancer Hospital
🇺🇸
Salt Lake City, Utah, United States
Mayo Clinic (AZ)
🇺🇸
Scottsdale, Arizona, United States
The University of Arizona Cancer Center - North Campus
🇺🇸
Tucson, Arizona, United States
Cancer Treatment Centers of America Zion, IL
🇺🇸
Zion, Illinois, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Hospital of the University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Sidney Kimmel Cancer Center at Jefferson
🇺🇸
Philadelphia, Pennsylvania, United States
University of Virginia Cancer Center
🇺🇸
Charlottesville, Virginia, United States
Mary Crowley Cancer Research - Medical City
🇺🇸
Dallas, Texas, United States
Royal Melbourne Hospital
🇦🇺
Melbourne, Australia
University of Wisconsin Clinical Science Center
🇺🇸
Madison, Wisconsin, United States
Rennes, Centre Eugène Marquis
🇫🇷
Rennes cedex, France
The Chinese University of Hong Kong
🇭🇰
Sha Tin, Hong Kong
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
🇮🇹
Milano, Italy
Tohoku University Hospital
🇯🇵
Miyagi, Japan
Kyoto University Hospital, Department of Clinical Pharmacology and Therapeutics
🇯🇵
Kyoto, Japan
Hospital Clinic i Provincial de Barcelona,
🇪🇸
Barcelona, Spain
National Taiwan University Hospital
🇨🇳
Taipei, Taiwan
City of Hope National Medical Center
🇺🇸
Duarte, California, United States
Guy's and St Thomas' NHS Foundation Trust
🇬🇧
London, United Kingdom