Futibatinib in Patients With Specific FGFR Aberrations

Study Overview
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Brief Summary
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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
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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.

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

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

Intervention / Treatment
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* Drug: Futibatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amplification, Futibatinib, Gastric cancer, Gastro-esophageal junction cancer, Solid tumor, Myeloid neoplasm, Lymphoid neoplasm, FGFR, Rearrangement, TAS-120