Futibatinib in Patients With Specific FGFR Aberrations

Advanced or Metastatic Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04189445
• Other study ID #: TAS-120-202
• Secondary ID: 2019-004084-49
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 24, 2020
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Taiho Oncology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 115
• Est. completion date: December 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Advanced or Metastatic Gastric or Gastroesophageal Cancer
• Advanced or Metastatic Solid Tumor
• Myeloid or Lymphoid Neoplasms (MLN)
• Neoplasms

Intervention

Drug:
• Futibatinib
Futibatinib tablets will be dosed orally every day on a continuous 28-day cycle

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Bruxelles
France	Institut Bergonié	Bordeaux	Gironde
France	Centre Georges François Leclerc	Dijon	Côte-d'Or
France	Centre Léon Bérard	Lyon	Rhone
France	Centre Antoine Lacassagne	Nice	Alpes Maritimes
France	Hôpital Saint-Louis	Paris Cedex 10	Paris
France	Centre Hospitalier Lyon Sud	Pierre Benite cedex	Rhone
France	Centre Paul Strauss	Strasbourg	Bas Rhin
France	Institut Gustave Roussy	Villejuif	Val De Marne
Germany	Universitaetsklinikum Freiburg	Freiburg	Baden Wuerttemberg
Germany	Universitaetsklinikum Heidelberg	Heidelberg	Baden Wuerttemberg
Germany	Universitaetsklinikum Koeln	Koeln	Nordrhein Westfalen
Hong Kong	The University of Hong Kong	Hong Kong
Hong Kong	Hong Kong United Oncology Centre	Jordon
Italy	Azienda Ospedaliera Universitaria Careggi	Florence
Italy	Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori	Meldola	Forli - Cesena
Italy	IEO Istituto Europeo di Oncologia	Milano
Italy	Ospedale Sacro Cuore Don Calabria	Negrar	Verona
Italy	Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Trento)	Verona
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo-To
Japan	National Cancer Center Hospital East	Kashiwa-shi	Chiba-Ken
Japan	NHO Shikoku Cancer Center	Matsuyama-shi	Ehime-Ken
Japan	Aichi Cancer Center Hospital	Nagoya-shi	Aichi-Ken
Japan	Hokkaido University Hospital	Sapporo-shi	Hokkaido
Japan	Osaka University Hospital	Suita-shi	Osaka-Fu
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seul
Korea, Republic of	Seoul National University Hospital	Seul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seul
Netherlands	Antoni van Leeuwenhoek	Amsterdam
Netherlands	Erasmus Medisch Centrum	Rotterdam
Portugal	Centro Hospitalar de Lisboa Central, E.P.E. - Hospital de Santo António dos Capuchos	Lisboa
Portugal	Fundação Champalimaud	Lisboa
Portugal	Centro Hospitalar do Porto, E.P.E - Hospital de Santo Antonio	Porto
Singapore	National University Cancer Institute	Singapore
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario HM Madrid Sanchinarro	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Clinica Universidad de Navarra	Pamplona
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Spain	Instituto Valenciano de Oncologia IVO	Valencia
Sweden	Karolinska universitetssjukhuset - Solna	Solna
Sweden	Akademiska Sjukhuset	Uppsala
Turkey	Acibadem Adana Hospital	Adana
Turkey	Acibadem Maslak Hospital	Istanbul
Turkey	Namik Kemal University	Tekirdag
United Kingdom	Sarah Cannon Research Institute UK	London	Greater London
United States	University of Maryland	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Houston Methodist Cancer Center	Houston	Texas
United States	The University of Texas M. D. Anderson Cancer Center	Houston	Texas
United States	UCLA Medical Center	Los Angeles	California
United States	Mercy Clinic Oncology and Hematology - Coletta	Oklahoma City	Oklahoma
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Georgetown University - Lombardi Comprehensive Cancer Center	Washington	District of Columbia
United States	Henry Ford Hospital	Woodhaven	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Taiho Oncology, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Portugal,  Singapore,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	CR+CRi rate in Cohort C	CR+CRi rate, defined as the proportion of patients who achieved a CR or CRi	Approximately 6 months
Secondary	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
Secondary	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
Secondary	Complete cytogenetic response (CCyR) rate in Cohort C.	CCyR rate, defined as the proportion of patients who achieved a CCyR	Approximately 6 months
Secondary	Partial cytogenetic response (PCyR) rate in Cohort C	PCyR rate, defined as the proportion of patients who achieved a PCyR	Approximately 6 months
Secondary	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
Secondary	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
Secondary	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