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

• ClinicalTrials.gov Identifier: NCT02052778
• Recruitment Status: Completed
• First Posted: February 3, 2014
• Results First Posted: March 20, 2024
• Last Update Posted: March 20, 2024
• Sponsor: Taiho Oncology, Inc.
• Information provided by (Responsible Party): Taiho Oncology, Inc.

Tracking Information

• First Submitted Date: January 23, 2014
• First Posted Date: February 3, 2014
• Results First Submitted Date: September 27, 2023
• Results First Posted Date: March 20, 2024
• Last Update Posted Date: March 20, 2024
• Actual Study Start Date: July 21, 2014
• Actual Primary Completion Date: October 1, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 20, 2024)

• Phase 1: Dose Escalation-Maximum Tolerated Dose (MTD) [ Time Frame: 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 [ Time Frame: 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 [ 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 ]
  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 [ Time Frame: 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.

Original Primary Outcome Measures (submitted: January 30, 2014)

• Safety and tolerability of TAS-120 [ Time Frame: Safety monitoring will begin at the time of the first dose of TAS-120, and will continue for 30 days after the last dose of TAS-120, until the initiation of another anticancer therapy, or up to 4 years, whichever occurs first. ]
  Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 4.03) will be used. Assessed by number and severity of adverse events, physical exam, vital signs, weight, ECOG Performance Status, urinalysis, ophthalmological examination, neurological examination: electrocardiogram evaluation, hematology and coagulation, serum chemistry.
• Tumor assessments according to RECIST guidelines (version 1.1, 2009) [ Time Frame: Computed tomography scans will be performed at week 6, 12 and every 9 weeks thereafter until until treatment discontinuation, or up to 4 years, whichever occurs first. ]
  The determination of antitumor efficacy will be based on objective tumor assessments made by the investigator according to the revised RECIST guidelines (version 1.1, 2009) of unidimensional evaluation.
• Multiple Myeloma Assessments [ Time Frame: Multiple myeloma assessments for response will be conducted at the beginning of each cycle, i.e. every 3 weeks, until treatment discontinuation, or up to 4 years, whichever occurs first. ]
  Serum, urine protein electrophoresis and serum free light chain(SPEP/UPEP/SFLC) will be obtain to assess Multiple myeloma using The International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma (Durie et al, 2006).

Current Secondary Outcome Measures (submitted: February 20, 2024)

• Phase 1: Dose Expansion: Duration of Response (DOR) [ 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 ]
  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) [ Time Frame: 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) [ 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 ]
  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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ 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]) ]
  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 [ 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]) ]
  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 [ 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]) ]
  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 [ 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]) ]
  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 [ 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]) ]
  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 [ 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]) ]
  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 [ 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]) ]
  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) [ Time Frame: 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) [ Time Frame: 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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of TAS-120 in Patients With Advanced Solid Tumors
• Official Title: Phase 1/2 Study of TAS-120 in Patients With Advanced Solid Tumors Harboring FGF/FGFR Aberrations

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 Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

Drug: Futibatinib

oral once daily dosing, 21-day cycle

Other Name: TAS-120

Study Arms

• Experimental: Phase 1: Dose Escalation: QOD Dosing: 8 mg
  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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: Phase 1: Dose Expansion: Sub-cohort 1
  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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib
• Experimental: 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.
  Intervention: Drug: Futibatinib

• Publications *: Bahleda R, Meric-Bernstam F, Goyal L, Tran B, He Y, Yamamiya I, Benhadji KA, Matos I, Arkenau HT. Phase I, first-in-human study of futibatinib, a highly selective, irreversible FGFR1-4 inhibitor in patients with advanced solid tumors. Ann Oncol. 2020 Oct;31(10):1405-1412. doi: 10.1016/j.annonc.2020.06.018. Epub 2020 Jul 2.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 20, 2024): 407
• Original Estimated Enrollment (submitted: January 30, 2014): 835
• Actual Study Completion Date: May 29, 2021
• Actual Primary Completion Date: October 1, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Netherlands, Spain, Taiwan, United Kingdom, United States
• Removed Location Countries: Portugal

Administrative Information

• NCT Number: NCT02052778
• Other Study ID Numbers: TPU-TAS-120-101; 2013-004810-16 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Taiho Oncology, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Taiho Oncology, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Taiho Oncology, Inc.
• Verification Date: February 2024