Futibatinib in Patients With Specific FGFR Aberrations

Phase 2

Terminated

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

Interventions: Drug: Futibatinib

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: TERMINATED

Sex: All

Target Recruitment: 115

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:
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.
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	Participants with advanced or metastatic solid tumors harboring FGFR1-4 rearrangements received futibatinib 20 mg, oral tablets, once a day on a continuous 28-day cycle up to a maximum of 841 days.
Futibatinib (Cohort B)	Futibatinib	Participants with advanced or metastatic solid gastric or GEJ cancer harboring FGFR2 amplification received futibatinib 20 mg, oral tablets, once a day on a continuous 28-day cycle up to a maximum of 297 days.
Futibatinib (Cohort C)	Futibatinib	Participants with myeloid or lymphoid neoplasm harboring FGFR1 rearrangement were to receive futibatinib 20 mg, oral tablets, once a day on a continuous 28-day cycle until disease progression, unacceptable toxicity or other treatment discontinuation criteria are met.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) Based on Independent Central Review (IRC) in Cohorts A and B	At the end of every 2 cycles until disease progression (Up to 31 months)	ORR was defined as the percentage of participants 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 IRC of radiological images. CR was defined as disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. ORR was calculated based on the best overall response recorded from the start of treatment until progressive disease or start of subsequent new anticancer treatment. Percentages were rounded off to the nearest single decimal place.
Complete Response (CR) Rate in Cohort C	At the end of every 2 cycles until disease progression (Up to 31 months)	CR rate was defined as the percentage of participants who achieved a CR (per response criteria for myeloid or lymphoid neoplasm) based on investigator assessment of imaging, peripheral blood, and bone marrow. CR was defined as disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to \<10 mm.

Secondary Outcome Measures

Name	Time	Method
ORR Based on Investigator Assessment in Cohorts A and B	At the end of every 2 cycles until disease progression (Up to 31 months)	ORR was defined as the percentage of participants experiencing a best overall response of PR or CR (per RECIST 1.1), based on investigator assessment. CR was defined as disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. ORR was calculated based on the best overall response recorded from the start of treatment until progressive disease or start of subsequent new anticancer treatment. Percentages were rounded off to the nearest single decimal place.
Duration of Response (DOR) Based on IRC in Cohorts A, B and C	At the end of every 2 cycles until disease progression (Up to 31 months)	DOR was defined as the time from the first documentation of response (CR or PR in based on IRC) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first. CR was defined as disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. DOR was estimated using the Kaplan-Meier method.
DOR Based on Investigator Assessment in Cohorts A, B and C	At the end of every 2 cycles until disease progression (Up to 31 months)	DOR was defined as the time from the first documentation of response (CR or PR in based on Investigator Assessment) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first. CR was defined as disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. DOR was estimated using the Kaplan-Meier method.
Progression- Free Survival (PFS) Based on IRC in Cohorts A, B and C	At the end of every 2 cycles until disease progression (Up to 31 months)	PFS was defined as the time from first dose of the study therapy to the date of death (any cause) or disease progression (based on IRC), whichever occurs first. The PFS was analyzed using a Kaplan-Meier method, with PFS time being censored on the date of the last disease assessment. The 95% CI for median PFS was provided using the Kaplan-Meier procedure.
PFS Based on Investigator Review in Cohorts A, B and C	At the end of every 2 cycles until disease progression (Up to 31 months)	PFS was defined as the time from first dose of the study therapy to the date of death (any cause) or disease progression (based on Investigator Review), whichever occurs first. The PFS was analyzed using a Kaplan-Meier method, with PFS time being censored on the date of the last disease assessment. The 95% CI for median PFS was provided using the Kaplan-Meier procedure.
Overall Survival (OS) in Cohorts A, B and C	Up to 31 months	OS was defined as the time from the date of first dose to the death date. Participants without a documented death date were censored on the last date they were known to be alive. The OS was presented using a Kaplan-Meier estimate. The 95% CI for median OS was provided using the Kaplan-Meier procedure.
Disease Control Rate (DCR) Based on IRC in Cohort A and B	At the end of every 2 cycles until disease progression (Up to 31 months)	DCR was defined as the percentage of participants experiencing a best overall response of stable disease (SD), PR, or CR (per RECIST 1.1), based on IRC. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), referencing the smallest sum diameters while on study. PD was defined as at least a 20% increase in the sum of target lesion diameters from the smallest on study (including baseline), with an absolute increase of ≥ 5 mm, or the appearance of new lesions. CR was defined as disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. Percentages were rounded off to the nearest single decimal place.
DCR Based on Investigator Review in Cohort A and B	At the end of every 2 cycles until disease progression (Up to 31 months)	DCR was defined as the percentage of participants experiencing a best overall response of SD, PR, or CR (per RECIST 1.1), based on IRC. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, referencing the smallest sum diameters while on study. PD was defined as at least a 20% increase in the sum of target lesion diameters from the smallest on study (including baseline), with an absolute increase of ≥ 5 mm, or the appearance of new lesions. CR was defined as disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. Percentages were rounded off to the nearest single decimal place.
CR+ Complete Response With Incomplete Hematological Recovery (CRi) Rate in Cohort C	Up to 31 months	CR+CRi rate was defined as the percentage of participants who achieved a CR or CRi.
Duration of CR in Cohort C	Up to 31 months	Duration of CR was 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.
Duration of CR+CRi in Cohort C	Up to 31 months	Duration of CR+CRi was 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.
Complete Cytogenetic Response (CCyR) Rate in Cohort C	Up to 31 months	CCyR rate was defined as the percentage of participants who achieved a CCyR.
Partial Cytogenetic Response (PCyR) Rate in Cohort C	Up to 31 months	PCyR rate was defined as the percentage of participants who achieved a PCyR.
Relapse-free Survival (RFS) in Cohort C	Up to 31 months	RFS was 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	Up to 31 months	EFS was defined as the time from first dose of study therapy to treatment failure, disease relapse after CR, or participant death due to any cause, whichever occurs first.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) - Cohort A, B and C	From the first dose of study drug up to 30 days after the last dose (Up to 31 months)	An adverse event (AE) is defined as any untoward medical occurrence in a clinical study participant and does not necessarily have a causal relationship with the study drug. A treatment-emergent AE (TEAE) is defined as an AE that is starting or worsening at the time of or after the first dose of study drug administration and within 30 days after the last dose of study drug, and does not necessarily have a causal relationship to the use of the study drug.

Trial Locations

Locations (61): Banner MD Anderson Cancer Center
🇺🇸
Gilbert, Arizona, United States
UCLA Medical Center
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Los Angeles, California, United States
Georgetown University - Lombardi Comprehensive Cancer Center
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Washington D.C., District of Columbia, United States
University of Chicago Comprehensive Cancer Center
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Chicago, Illinois, United States
University of Maryland
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Baltimore, Maryland, United States
Beth Israel Deaconess Medical Center
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Boston, Massachusetts, United States
Henry Ford Hospital
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Woodhaven, Michigan, United States
Mercy Clinic Oncology and Hematology - Coletta
🇺🇸
Oklahoma City, Oklahoma, United States
Fox Chase Cancer Center
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Philadelphia, Pennsylvania, United States
Houston Methodist Cancer Center
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Houston, Texas, United States
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Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States