Futibatinib in Patients With Specific FGFR Aberrations
- Conditions
- Advanced or Metastatic Gastric or Gastroesophageal CancerAdvanced or Metastatic Solid TumorMyeloid or Lymphoid Neoplasms (MLN)
- Interventions
- Registration Number
- NCT04189445
- Lead Sponsor
- Taiho Oncology, Inc.
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 115
-
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
-
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
-
History and/or current evidence of any of the following disorders:
- Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically significant in the opinion of the Investigator
- 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
- Retinal or corneal disorder confirmed by retinal/corneal examination and considered clinically significant in the opinion of the Investigator.
-
Prior treatment with an FGFR inhibitor
-
Brain metastases that are untreated or clinically or radiologically unstable (that is, have been stable for <1 month)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Futibatinib (Cohort A) Futibatinib Advanced or metastatic solid tumors harboring FGFR1-4 rearrangements Futibatinib (Cohort C) Futibatinib Myeloid or lymphoid neoplasm harboring FGFR1 rearrangement Futibatinib (Cohort B) Futibatinib Advanced or metastatic solid gastric or GEJ cancer harboring FGFR2 amplification
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) in Cohorts A and B Approximately 6 months 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.
Complete response (CR) rate in Cohort C Approximately 6 months 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.
- Secondary Outcome Measures
Name Time Method Duration of CR in Cohort C Approximately 6 months 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.
Disease control rate (DCR) in Cohort A and B Approximately 6 months 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).
ORR based on investigator assessment ORR in Cohorts A and B Approximately 6 months 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.
Overall Survival (OS) in Cohorts A, B and C Approximately 12 months OS, defined as the time from the date of first dose to the death date.
Duration of CR+CRi in Cohort C Approximately 6 months 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.
Partial cytogenetic response (PCyR) rate in Cohort C Approximately 6 months PCyR rate, defined as the proportion of patients who achieved a PCyR
Duration of Response (DOR) in Cohorts A, B and C Approximately 6 months 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.
Complete cytogenetic response (CCyR) rate in Cohort C. Approximately 6 months CCyR rate, defined as the proportion of patients who achieved a CCyR
To assess the safety and tolerability in Cohorts A, B and C Approximately 6 months 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.
Progression- free survival (PFS) in Cohorts A, B and C Approximately 6 months 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.
CR+CRi rate in Cohort C Approximately 6 months CR+CRi rate, defined as the proportion of patients who achieved a CR or CRi
Relapse-free survival (RFS) in Cohort C Approximately 6 months 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
Event-free survival (EFS) in Cohort C Approximately 6 months 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
Trial Locations
- Locations (61)
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Chiba-Ken, Japan
Mercy Clinic Oncology and Hematology - Coletta
🇺🇸Oklahoma City, Oklahoma, United States
Ospedale Sacro Cuore Don Calabria
🇮🇹Negrar, Verona, Italy
Centre Georges François Leclerc
🇫🇷Dijon, Côte-d'Or, France
Georgetown University - Lombardi Comprehensive Cancer Center
🇺🇸Washington, District of Columbia, United States
Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
🇮🇹Meldola, Forli - Cesena, Italy
Centre Léon Bérard
🇫🇷Lyon, Rhone, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre Benite cedex, Rhone, France
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Baden Wuerttemberg, Germany
Azienda Ospedaliera Universitaria Careggi
🇮🇹Florence, Italy
Aichi Cancer Center Hospital
🇯🇵Nagoya-shi, Aichi-Ken, Japan
Centre Antoine Lacassagne
🇫🇷Nice, Alpes Maritimes, France
Universitaetsklinikum Freiburg
🇩🇪Freiburg, Baden Wuerttemberg, Germany
Universitaetsklinikum Koeln
🇩🇪Koeln, Nordrhein Westfalen, Germany
The University of Hong Kong
🇭🇰Hong Kong, Hong Kong
Seoul National University Hospital
🇰🇷Seul, Korea, Republic of
Hôpital Saint-Louis
🇫🇷Paris Cedex 10, Paris, France
Osaka University Hospital
🇯🇵Suita-shi, Osaka-Fu, Japan
Institut Gustave Roussy
🇫🇷Villejuif, Val De Marne, France
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo-To, Japan
Samsung Medical Center
🇰🇷Seul, Korea, Republic of
Fundação Champalimaud
🇵🇹Lisboa, Portugal
Centro Hospitalar do Porto, E.P.E - Hospital de Santo Antonio
🇵🇹Porto, Portugal
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Henry Ford Hospital
🇺🇸Woodhaven, Michigan, United States
Houston Methodist Cancer Center
🇺🇸Houston, Texas, United States
Institut Jules Bordet
🇧🇪Bruxelles, Belgium
The University of Texas M. D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Centre Paul Strauss
🇫🇷Strasbourg, Bas Rhin, France
Institut Bergonié
🇫🇷Bordeaux, Gironde, France
IEO Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Trento)
🇮🇹Verona, Italy
NHO Shikoku Cancer Center
🇯🇵Matsuyama-shi, Ehime-Ken, Japan
Hokkaido University Hospital
🇯🇵Sapporo-shi, Hokkaido, Japan
Seoul National University Bundang Hospital
🇰🇷Seongnam, Gyeonggi-do, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Severance Hospital, Yonsei University Health System
🇰🇷Seul, Korea, Republic of
Antoni van Leeuwenhoek
🇳🇱Amsterdam, Netherlands
National University Cancer Institute
🇸🇬Singapore, Singapore
Erasmus Medisch Centrum
🇳🇱Rotterdam, Netherlands
Centro Hospitalar de Lisboa Central, E.P.E. - Hospital de Santo António dos Capuchos
🇵🇹Lisboa, Portugal
Clinica Universidad de Navarra
🇪🇸Pamplona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Karolinska universitetssjukhuset - Solna
🇸🇪Solna, Sweden
Instituto Valenciano de Oncologia IVO
🇪🇸Valencia, Spain
Akademiska Sjukhuset
🇸🇪Uppsala, Sweden
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Acibadem Adana Hospital
🇹🇷Adana, Turkey
Acibadem Maslak Hospital
🇹🇷Istanbul, Turkey
Namik Kemal University
🇹🇷Tekirdağ, Turkey
Sarah Cannon Research Institute UK
🇬🇧London, Greater London, United Kingdom
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario HM Madrid Sanchinarro
🇪🇸Madrid, Spain
Hong Kong United Oncology Centre
🇭🇰Jordon, Hong Kong