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

NCT ID: NCT02052778

Last Updated: 2025-03-27

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

407 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-07-21

Study Completion Date

2024-10-22

Brief Summary

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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

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Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

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.

Group Type EXPERIMENTAL

Futibatinib

Intervention Type DRUG

oral once daily dosing, 21-day cycle

Interventions

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Futibatinib

oral once daily dosing, 21-day cycle

Intervention Type DRUG

Other Intervention Names

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TAS-120

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Taiho Oncology, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status

Mayo Clinic (AZ)

Scottsdale, Arizona, United States

Site Status

The University of Arizona Cancer Center - North Campus

Tucson, Arizona, United States

Site Status

City of Hope National Medical Center

Duarte, California, United States

Site Status

UCSF Helen Diller Family Comprehensive Cancer Center. Mission Bay

San Francisco, California, United States

Site Status

Cancer Treatment Centers of America

Newnan, Georgia, United States

Site Status

Cancer Treatment Centers of America Zion, IL

Zion, Illinois, United States

Site Status

The University of Kansas Cancer Center

Fairway, Kansas, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institution

Boston, Massachusetts, United States

Site Status

Wayne State Universtity (Karmanos Cancer Institute)

Detroit, Michigan, United States

Site Status

Mayo Clinic (MN)

Rochester, Minnesota, United States

Site Status

New Mexico Cancer Care Alliancer

Albuquerque, New Mexico, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Sidney Kimmel Cancer Center at Jefferson

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Greenville Health System ITOR,Clinical Research Unit

Greenville, South Carolina, United States

Site Status

Spartanburg Medical Center

Spartanburg, South Carolina, United States

Site Status

Mary Crowley Cancer Research - Medical City

Dallas, Texas, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Utah, Huntsman Cancer Hospital

Salt Lake City, Utah, United States

Site Status

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Site Status

Virginia Mason Cancer Center

Seattle, Washington, United States

Site Status

University of Wisconsin Clinical Science Center

Madison, Wisconsin, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Royal Melbourne Hospital

Melbourne, , Australia

Site Status

Sunnybrook Research Institue

Toronto, , Canada

Site Status

Centre Léon Bérard Bât

Lyon, Cedex, France

Site Status

Institut Bergonie

Bordeaux, , France

Site Status

Hospices Civils de Lyon

Bron, , France

Site Status

Pitié-Salpêtrière Hospital

Paris, , France

Site Status

Rennes, Centre Eugène Marquis

Rennes, , France

Site Status

Institute Goustave-Roussy-DITEP

Villejuif, , France

Site Status

University Hospital Essen, West German Cancer Center, Department of Medical Oncology

Essen, , Germany

Site Status

The Chinese University of Hong Kong

Shatin, , Hong Kong

Site Status

Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

Milan, , Italy

Site Status

UOC Oncologia Medica 1 I"V - Istituto Oncologico Veneto - IRCCS

Padua, , Italy

Site Status

Hokkaido University Hospital

Hokkaido, , Japan

Site Status

Kyoto University Hospital, Department of Clinical Pharmacology and Therapeutics

Kyoto, , Japan

Site Status

Tohoku University Hospital

Miyagi, , Japan

Site Status

Osaka International Cancer Institute

Osaka, , Japan

Site Status

National Cancer Center Hospital

Tokyo, , Japan

Site Status

University Hospital Jenna

Jenna, , Netherlands

Site Status

Yonsei University, Severance Hospital (Seoul)

Seoul, , South Korea

Site Status

ASAN Medical Center (Seoul)

Seoul, , South Korea

Site Status

Samsung Medical Center (Seoul)

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Val D'Hebron University Hospital

Barcelona, , Spain

Site Status

Hospital Clinic i Provincial de Barcelona,

Barcelona, , Spain

Site Status

University Hospital Ramón y Cajal

Madrid, , Spain

Site Status

Centro Integral Oncológico Clara Campal - Hospital Universitario Madrid Sanchinarro

Madrid, , Spain

Site Status

Cheng Kung University Hospital

Tainan City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Guy's and St Thomas' NHS Foundation Trust

London, , United Kingdom

Site Status

Sarah Cannon Research Institute

London, , United Kingdom

Site Status

University College London Hospital

London, , United Kingdom

Site Status

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

Countries

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United States Australia Canada France Germany Hong Kong Italy Japan Netherlands South Korea Spain Taiwan United Kingdom

References

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Goyal L, Meric-Bernstam F, Hollebecque A, Valle JW, Morizane C, Karasic TB, Abrams TA, Furuse J, Kelley RK, Cassier PA, Klumpen HJ, Chang HM, Chen LT, Tabernero J, Oh DY, Mahipal A, Moehler M, Komatsu Y, Ahn DH, Epstein RS, Halim AB, Wacheck V, He Y, Liu M, Benhadji KA, Bridgewater JA; FOENIX-CCA2 Study Investigators. Plain language summary of the FOENIX-CCA2 study: futibatinib for people with advanced bile duct cancer. Future Oncol. 2024;20(36):2811-2822. doi: 10.1080/14796694.2024.2364504. Epub 2024 Jun 17.

Reference Type DERIVED
PMID: 38884254 (View on PubMed)

DiPeri TP, Zhao M, Evans KW, Varadarajan K, Moss T, Scott S, Kahle MP, Byrnes CC, Chen H, Lee SS, Halim AB, Hirai H, Wacheck V, Kwong LN, Rodon J, Javle M, Meric-Bernstam F. Convergent MAPK pathway alterations mediate acquired resistance to FGFR inhibitors in FGFR2 fusion-positive cholangiocarcinoma. J Hepatol. 2024 Feb;80(2):322-334. doi: 10.1016/j.jhep.2023.10.041. Epub 2023 Nov 14.

Reference Type DERIVED
PMID: 37972659 (View on PubMed)

Goyal L, Meric-Bernstam F, Hollebecque A, Valle JW, Morizane C, Karasic TB, Abrams TA, Furuse J, Kelley RK, Cassier PA, Klumpen HJ, Chang HM, Chen LT, Tabernero J, Oh DY, Mahipal A, Moehler M, Mitchell EP, Komatsu Y, Masuda K, Ahn D, Epstein RS, Halim AB, Fu Y, Salimi T, Wacheck V, He Y, Liu M, Benhadji KA, Bridgewater JA; FOENIX-CCA2 Study Investigators. Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma. N Engl J Med. 2023 Jan 19;388(3):228-239. doi: 10.1056/NEJMoa2206834.

Reference Type DERIVED
PMID: 36652354 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32622884 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2013-004810-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TPU-TAS-120-101

Identifier Type: -

Identifier Source: org_study_id

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