Futibatinib in Patients With Specific FGFR Aberrations

A Phase 2 Study of Futibatinib in Patients With Specific FGFR Aberrations

The purpose of this study is to evaluate the efficacy and safety of futibatinib in patients with FGFR aberrations in 3 distinct cohorts. Patients will be enrolled into one of 3 cohorts: patients with advanced, metastatic or locally-advanced solid tumors harboring FGFR1-4 rearrangements (excluding primary brain tumors and intrahepatic cholangiocarcinoma [iCCA]); patients with gastric or gastro-esophageal junction (GEJ) cancer harboring FGFR2 amplification; and patients with myeloid or lymphoid neoplasms with FGFR1 rearrangements.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced or Metastatic Solid Tumor; Advanced or Metastatic Gastric or Gastroesophageal Cancer; Myeloid or Lymphoid Neoplasms (MLN)
• Intervention / Treatment: Drug: Futibatinib

Detailed Description

Study TAS-120-202 is an open-label, multinational, 3-arm Phase 2 study evaluating the efficacy, safety, tolerability, PK, and pharmacodynamics of futibatinib in patients with FGFR aberrations. Eligible patients will be assigned to 1 of 3 treatment cohorts based on diagnosis and FGFR gene aberration status.

Patients will receive futibatinib at an oral dose of 20 mg once a day on a continuous 28-day cycle.

The study will enroll approximately:

• Cohort A: 60 patients with locally advanced, advanced, or metastatic solid tumor harboring FGFR rearrangements other than primary brain tumor or iCCA;
• Cohort B: 35 patients with locally-advanced, advanced, or metastatic gastric cancer or gastro-esophageal junction (GEJ) with FGFR2 amplification;
• Cohort C: 20 patients with myeloid or lymphoid neoplasms (MLN) with FGFR1 rearrangements

Treatment in all cohorts will continue until disease progression, unacceptable toxicity, or any other of the criteria for treatment discontinuation is met. For patients who discontinue treatment for reasons other than disease progression, tumor assessments should be continued until radiologic disease progression is documented or until initiation of subsequent new anticancer therapy (whichever occurs first).

Patients will be followed for survival every 12 weeks (±2 weeks) until survival events (deaths) have been reported for 75% of enrolled patients or the study is terminated early by the Sponsor.

Additional cohorts may be added in the future in case of new emerging efficacy data.

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1000
    • Institut Jules Bordet
• France
  • Alpes Maritimes
    • Nice, Alpes Maritimes, France, 06200
      • Centre Antoine Lacassagne
  • Bas Rhin
    • Strasbourg, Bas Rhin, France, 67000
      • Centre Paul Strauss
  • Côte-d'Or
    • Dijon, Côte-d'Or, France, 21079
      • Centre Georges Francois Leclerc
  • Gironde
    • Bordeaux, Gironde, France, 33076
      • Institut Bergonie
  • Paris
    • Paris Cedex 10, Paris, France, 75475
      • Hôpital Saint-Louis
  • Rhone
    • Lyon, Rhone, France, 69008
      • Centre Leon Berard
    • Pierre Benite cedex, Rhone, France, 69495
      • Centre Hospitalier Lyon Sud
  • Val De Marne
    • Villejuif, Val De Marne, France, 94805
      • Institut Gustave Roussy
• Germany
  • Baden Wuerttemberg
    • Freiburg, Baden Wuerttemberg, Germany, 79106
      • Universitaetsklinikum Freiburg
    • Heidelberg, Baden Wuerttemberg, Germany, 69120
      • Universitaetsklinikum Heidelberg
  • Nordrhein Westfalen
    • Koeln, Nordrhein Westfalen, Germany, 50924
      • Universitaetsklinikum Koeln
• Hong Kong
  • Hong Kong, Hong Kong
    • The University of Hong Kong
  • Jordon, Hong Kong, 0000
    • Hong Kong United Oncology Centre
• Italy
  • Florence, Italy, 50134
    • Azienda Ospedaliera Universitaria Careggi
  • Milano, Italy, 20141
    • IEO Istituto Europeo di Oncologia
  • Verona, Italy, 37124
    • Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Trento)
  • Forli - Cesena
    • Meldola, Forli - Cesena, Italy, 47014
      • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Verona
    • Negrar, Verona, Italy, 37024
      • Ospedale Sacro Cuore Don Calabria
• Japan
  • Aichi-Ken
    • Nagoya-shi, Aichi-Ken, Japan, 464-8681
      • Aichi Cancer Center Hospital
  • Chiba-Ken
    • Kashiwa-shi, Chiba-Ken, Japan, 277-8577
      • National Cancer Center Hospital East
  • Ehime-Ken
    • Matsuyama-shi, Ehime-Ken, Japan, 791-0280
      • NHO Shikoku Cancer Center
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Osaka-Fu
    • Suita-shi, Osaka-Fu, Japan, 565-0871
      • Osaka University Hospital
  • Tokyo-To
    • Chuo-ku, Tokyo-To, Japan, 104-0045
      • National Cancer Center Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Gyeonggi-do
    • Seongnam, Gyeonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Antoni van Leeuwenhoek
  • Rotterdam, Netherlands, 3015 AA
    • Erasmus Medisch Centrum
• Portugal
  • Lisboa, Portugal, 1169-050
    • Centro Hospitalar de Lisboa Central, E.P.E. - Hospital de Santo António dos Capuchos
  • Lisboa, Portugal, 4099-001
    • Fundação Champalimaud
  • Porto, Portugal, 4099-001
    • Centro Hospitalar do Porto, E.P.E - Hospital de Santo Antonio
• Singapore
  • Singapore, Singapore, 119074
    • National University Cancer Institute
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28050
    • Hospital Universitario HM Madrid Sanchinarro
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain, 46026
    • Hospital Universitari I Politècnic La Fe
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Valencia, Spain, 46009
    • Instituto Valenciano de Oncologia IVO
• Sweden
  • Solna, Sweden, 171 64
    • Karolinska Universitetssjukhuset - Solna
  • Uppsala, Sweden, 75185
    • Akademiska sjukhuset
• Turkey
  • Adana, Turkey, 01130
    • Acibadem Adana Hospital
  • Istanbul, Turkey, 34457
    • Acibadem Maslak Hospital
  • Tekirdağ, Turkey, 59100
    • Namik Kemal University
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, W1G 6AD
      • Sarah Cannon Research Institute UK
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234-2165
      • Banner MD Anderson Cancer Center
  • California
    • Los Angeles, California, United States, 90404
      • UCLA Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University - Lombardi Comprehensive Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02215-5400
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Woodhaven, Michigan, United States, 48183
      • Henry Ford Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Mercy Clinic Oncology and Hematology - Coletta
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 53705
      • Fox Chase Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas M. D. Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

2. Known FGFR aberration status and tumor type that meet all of the criteria for 1 of the following cohorts:

   a. Cohort A

   i. Histologically-confirmed, locally-advanced, advanced, or metastatic solid tumors harboring a FGFR1-4

ii. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

iii. Had disease progression/recurrence after standard treatment for their cancer

b. Cohort B

i. Histologically-confirmed, locally-advanced, advanced, or metastatic gastric or gastroesophageal junction cancer harboring a FGFR2 amplification.

ii. Measurable disease per RECIST 1.1

iii. Received at least 2 prior systemic regimens for advanced/metastatic disease

iv. Experienced disease progression/recurrence during or after the most recent prior systemic treatment for advanced/metastatic gastric cancer or GEJ cancer

c. Cohort C

i. Confirmed myeloid or lymphoid neoplasms as defined by WHO criteria with a FGFR1 rearrangement

ii. Not a candidate for hematological stem cell transplant (HSCT) or relapsed after HSCT and donor lymphocyte infusion, and progressed and not a candidate for other therapies

Exclusion Criteria:

1. History and/or current evidence of any of the following disorders:

   1. Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically significant in the opinion of the Investigator
   2. Ectopic mineralization/calcification including, but not limited to, soft tissue, kidneys, intestine, or myocardia and lung, considered clinically significant in the opinion of the Investigator
   3. Retinal or corneal disorder confirmed by retinal/corneal examination and considered clinically significant in the opinion of the Investigator.
2. Prior treatment with an FGFR inhibitor
3. Brain metastases that are untreated or clinically or radiologically unstable (that is, have been stable for <1 month)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Futibatinib (Cohort A); Advanced or metastatic solid tumors harboring FGFR1-4 rearrangements	Drug: Futibatinib; Futibatinib tablets will be dosed orally every day on a continuous 28-day cycle; Other Names: TAS-120
Experimental: Futibatinib (Cohort B); Advanced or metastatic solid gastric or GEJ cancer harboring FGFR2 amplification	Drug: Futibatinib; Futibatinib tablets will be dosed orally every day on a continuous 28-day cycle; Other Names: TAS-120
Experimental: Futibatinib (Cohort C); Myeloid or lymphoid neoplasm harboring FGFR1 rearrangement	Drug: Futibatinib; Futibatinib tablets will be dosed orally every day on a continuous 28-day cycle; Other Names: TAS-120

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) in Cohorts A and B	ORR, defined as the proportion of patients experiencing a best overall response of partial response (PR) or complete response (CR) (per Response Evaluation Criteria in Solid Tumors, RECIST version 1.1), based on independent central review of radiological images.	Approximately 6 months
Complete response (CR) rate in Cohort C	CR rate, defined as the proportion of patients who achieved a CR (per response criteria for MLN) based on investigators' assessment of imaging, peripheral blood, and bone marrow.	Approximately 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR based on investigator assessment ORR in Cohorts A and B	ORR, defined as the proportion of patients experiencing a best overall response of partial response (PR) or complete response (CR) (per RECIST 1.1), based on investigator assessment.	Approximately 6 months
Duration of Response (DOR) in Cohorts A, B and C	DOR, defined as the time from the first documentation of response (CR or PR in Cohorts A and B; CR, PR, or CRi in Cohort C) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.	Approximately 6 months
Progression- free survival (PFS) in Cohorts A, B and C	PFS, defined as the time from first dose of the study therapy to the date of death (any cause) or disease progression, whichever occurs first.	Approximately 6 months
Overall Survival (OS) in Cohorts A, B and C	OS, defined as the time from the date of first dose to the death date.	Approximately 12 months
Disease control rate (DCR) in Cohort A and B	DCR, defined as the proportion of patients experiencing a best overall response of stable response (SD), PR, or complete response (CR) (per RECIST 1.1).	Approximately 6 months
CR+CRi rate in Cohort C	CR+CRi rate, defined as the proportion of patients who achieved a CR or CRi	Approximately 6 months
Duration of CR in Cohort C	Duration of CR, defined as the time from the first documentation of CR to the first documentation of recurrence or death due to any cause, whichever occurs first.	Approximately 6 months
Duration of CR+CRi in Cohort C	Duration of CR+CRi, defined as the time from the first documentation of CR or CRi to the first documentation of disease relapse or death due to any cause, whichever occurs first.	Approximately 6 months
Complete cytogenetic response (CCyR) rate in Cohort C.	CCyR rate, defined as the proportion of patients who achieved a CCyR	Approximately 6 months
Partial cytogenetic response (PCyR) rate in Cohort C	PCyR rate, defined as the proportion of patients who achieved a PCyR	Approximately 6 months
Relapse-free survival (RFS) in Cohort C	RFS, defined as the time from first documentation of CR to the date of death (any cause) or disease relapse or death due to any cause, whichever occurs first	Approximately 6 months
Event-free survival (EFS) in Cohort C	EFS, defined as the time from first dose of study therapy to treatment failure, disease relapse after CR, or patient death due to any cause, whichever occurs first	Approximately 6 months
To assess the safety and tolerability in Cohorts A, B and C	Safety based on reported AEs will be graded according to the National Cancer Institute- Common Terminology Criteria for Adverse events (NCI-CTCAE), Version 5.0.	Approximately 6 months

Collaborators and Investigators

• Sponsor: Taiho Oncology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2020
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: December 3, 2019
• First Submitted That Met QC Criteria: December 5, 2019
• First Posted (Actual): December 6, 2019

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Gastric cancer; Solid tumor; FGFR; Futibatinib; Rearrangement; TAS-120; Gastro-esophageal junction cancer; Myeloid neoplasm; Lymphoid neoplasm; Amplification
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Futibatinib
• Other Study ID Numbers: TAS-120-202; 2019-004084-49 (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