Clinical trial NCT04189445: Futibatinib in Patients With Specific FGFR Aberrations
Official title: A Phase 2 Study of Futibatinib in Patients With Specific FGFR Aberrations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced or Metastatic Solid Tumor
Advanced or Metastatic Gastric or Gastroesophageal Cancer
Myeloid or Lymphoid Neoplasms (MLN)
Keywords: Futibatinib
Gastric cancer
Gastro-esophageal junction cancer
Solid tumor
Myeloid neoplasm
Lymphoid neoplasm
FGFR
Amplification
Rearrangement
TAS-120
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2019-12-06
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study consists of independent 3 cohorts (Cohorts A, B and C) and there is no difference in the treatment regimen between the cohorts
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Objective response rate (ORR) in Cohorts A and B
timeFrame: Approximately 6 months
measure: Complete response (CR) rate in Cohort C
timeFrame: Approximately 6 months
Secondary outcomes:
measure: ORR based on investigator assessment ORR in Cohorts A and B
timeFrame: Approximately 6 months
measure: Duration of Response (DOR) in Cohorts A, B and C
timeFrame: Approximately 6 months
measure: Progression- free survival (PFS) in Cohorts A, B and C
timeFrame: Approximately 6 months
measure: Overall Survival (OS) in Cohorts A, B and C
timeFrame: Approximately 12 months
measure: Disease control rate (DCR) in Cohort A and B
timeFrame: Approximately 6 months
measure: CR+CRi rate in Cohort C
timeFrame: Approximately 6 months
measure: Duration of CR in Cohort C
timeFrame: Approximately 6 months
measure: Duration of CR+CRi in Cohort C
timeFrame: Approximately 6 months
measure: Complete cytogenetic response (CCyR) rate in Cohort C.
timeFrame: Approximately 6 months
measure: Partial cytogenetic response (PCyR) rate in Cohort C
timeFrame: Approximately 6 months
measure: Relapse-free survival (RFS) in Cohort C
timeFrame: Approximately 6 months
measure: Event-free survival (EFS) in Cohort C
timeFrame: Approximately 6 months
measure: To assess the safety and tolerability in Cohorts A, B and C
timeFrame: Approximately 6 months
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Washington
country: United States
facility: Georgetown University - Lombardi Comprehensive Cancer Center
state: District of Columbia
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Woodhaven
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Oklahoma City
country: United States
facility: Mercy Clinic Oncology and Hematology - Coletta
state: Oklahoma
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: Houston Methodist Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas M. D. Anderson Cancer Center
state: Texas
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Nice
country: France
facility: Centre Antoine Lacassagne
state: Alpes Maritimes
city: Strasbourg
country: France
facility: Centre Paul Strauss
state: Bas Rhin
city: Dijon
country: France
facility: Centre Georges François Leclerc
state: Côte-d'Or
city: Bordeaux
country: France
facility: Institut Bergonié
state: Gironde
city: Paris Cedex 10
country: France
facility: Hôpital Saint-Louis
state: Paris
city: Lyon
country: France
facility: Centre Léon Bérard
state: Rhone
city: Pierre Benite cedex
country: France
facility: Centre Hospitalier Lyon Sud
state: Rhone
city: Villejuif
country: France
facility: Institut Gustave Roussy
state: Val De Marne
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
state: Baden Wuerttemberg
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
state: Baden Wuerttemberg
city: Koeln
country: Germany
facility: Universitaetsklinikum Koeln
state: Nordrhein Westfalen
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong
city: Jordon
country: Hong Kong
facility: Hong Kong United Oncology Centre
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
state: Forli - Cesena
city: Negrar
country: Italy
facility: Ospedale Sacro Cuore Don Calabria
state: Verona
city: Florence
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Milano
country: Italy
facility: IEO Istituto Europeo di Oncologia
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Trento)
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center Hospital
state: Aichi-Ken
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba-Ken
city: Matsuyama-shi
country: Japan
facility: NHO Shikoku Cancer Center
state: Ehime-Ken
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Suita-shi
country: Japan
facility: Osaka University Hospital
state: Osaka-Fu
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo-To
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seul
country: Korea, Republic of
facility: Samsung Medical Center
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Central, E.P.E. - Hospital de Santo António dos Capuchos
city: Lisboa
country: Portugal
facility: Fundação Champalimaud
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto, E.P.E - Hospital de Santo Antonio
city: Singapore
country: Singapore
facility: National University Cancer Institute
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario HM Madrid Sanchinarro
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia IVO
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Solna
country: Sweden
facility: Karolinska universitetssjukhuset - Solna
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Adana
country: Turkey
facility: Acibadem Adana Hospital
city: Istanbul
country: Turkey
facility: Acibadem Maslak Hospital
city: Tekirdağ
country: Turkey
facility: Namik Kemal University
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
state: Greater London
Study officials:
References: