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

Phase 1/2 Study of TAS-120 in Patients With Advanced Solid Tumors Harboring FGF/FGFR Aberrations

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).

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Gastric Cancer; Cholangiocarcinoma; Urothelial Cancer; Primary CNS Tumors; Advanced and Metastatic Cancer Patients With Tumors Harboring FGF/FGFR Tumors
• Intervention / Treatment: Drug: Futibatinib

• Study Type: Interventional
• Enrollment (Actual): 407
• Phase: Phase 2; Phase 1

Expanded Access

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Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia
    • Royal Melbourne Hospital
• Canada
  • Toronto, Canada, M4N3M5
    • Sunnybrook Research Institue
• France
  • Bordeaux, France, 33076
    • Institut Bergonié
  • Bron, France, 69677
    • Hospices Civils de Lyon
  • Paris, France, 75013
    • Pitie-Salpêtrière Hospital
  • Rennes cedex, France, 35042
    • Rennes, Centre Eugène Marquis
  • Villejuif, France, 94805
    • Institute Goustave-Roussy-DITEP
  • Cedex
    • Lyon, Cedex, France, 69373
      • Centre Léon Bérard Bât
• Germany
  • Essen, Germany, 45147
    • University Hospital Essen, West German Cancer Center, Department of Medical Oncology
• Hong Kong
  • Sha Tin, Hong Kong
    • The Chinese University of Hong Kong
• Italy
  • Milano, Italy, 20133
    • Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
  • Padova, Italy, 35128
    • UOC Oncologia Medica 1 I"V - Istituto Oncologico Veneto - IRCCS
• Japan
  • Hokkaido, Japan, 060-8648
    • Hokkaido University Hospital
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital, Department of Clinical Pharmacology and Therapeutics
  • Miyagi, Japan, 980-8574
    • Tohoku University Hospital
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Yonsei University, Severance Hospital (Seoul)
  • Seoul, Korea, Republic of, 05505
    • ASAN Medical Center (Seoul)
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center (Seoul)
• Netherlands
  • Jenna, Netherlands, 07740
    • University Hospital Jenna
• Spain
  • Barcelona, Spain, 08035
    • Val D'Hebron University Hospital
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona,
  • Madrid, Spain, 28034
    • University Hospital Ramón Y Cajal
  • Madrid, Spain
    • Centro Integral Oncológico Clara Campal - Hospital Universitario Madrid Sanchinarro
• Taiwan
  • Tainan, Taiwan, 704
    • Cheng Kung University Hospital
  • Taipei, Taiwan, 10048
    • National Taiwan University Hospital
• United Kingdom
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute
  • London, United Kingdom, SE1 9RT
    • Guy's and St Thomas' NHS Foundation Trust
  • London, United Kingdom, W1T 7HA
    • University College London Hospital
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic (AZ)
    • Tucson, Arizona, United States, 85719
      • The University of Arizona Cancer Center - North Campus
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • San Francisco, California, United States, 94158
      • UCSF Helen Diller Family Comprehensive Cancer Center. Mission Bay
  • Georgia
    • Newnan, Georgia, United States, 30265
      • Cancer Treatment Centers of America
  • Illinois
    • Zion, Illinois, United States, 60099
      • Cancer Treatment Centers of America Zion, IL
  • Kansas
    • Fairway, Kansas, United States, 66205
      • The University of Kansas Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institution
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State Universtity (Karmanos Cancer Institute)
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic (MN)
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • New Mexico Cancer Care Alliancer
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Sidney Kimmel Cancer Center at Jefferson
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center Hillman Cancer Center
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System ITOR,Clinical Research Unit
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research - Medical City
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah, Huntsman Cancer Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Cancer Center
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Clinical Science Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

23

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120
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.	Drug: Futibatinib; oral once daily dosing, 21-day cycle; Other Names: TAS-120

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Cycle 1 (21-day cycle)
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.	Cycle 1 (21-day cycle)
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.	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
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.	Up to approximately 37.5 months (through cut-off date 29-May-2021)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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
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.	Up to approximately 37.5 months (through cut-off date 29-May-2021)
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.	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
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.	Up to approximately 37.5 months (through cut-off date 29-May-2021)
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.	up to approximately 27.5 months (through cut-off date 30-Jun-2019)
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.	Up to approximately 37.5 months (through cut-off date 29-May-2021)
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.	up to approximately 27.5 months (through cut-off date 30-Jun-2019)
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.	Up to approximately 37.5 months (through cut-off date 29-May-2021)
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.	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])
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.	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])
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.	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])
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.	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])
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.	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])
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.	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])
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.	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])
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.	From the first dose up to approximately 50.5 months (through cut-off date 29-May-2021)
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.	From the first dose up to approximately 37.5 months (through cut-off date 29-May-2021)

Collaborators and Investigators

• Sponsor: Taiho Oncology, Inc.
• Investigators: Study Director: Karim Benhadji, MD, Taiho Oncology, Inc.

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2014
• Primary Completion (Actual): October 1, 2020
• Study Completion (Actual): May 29, 2021

Study Registration Dates

• First Submitted: January 23, 2014
• First Submitted That Met QC Criteria: January 30, 2014
• First Posted (Estimated): February 3, 2014

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: FGFR; FGF; Futibatinib; TAS-120
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms; Cholangiocarcinoma; Antineoplastic Agents; Futibatinib
• Other Study ID Numbers: TPU-TAS-120-101; 2013-004810-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No