Futibatinib in Patients With Specific FGFR Aberrations

Taiho Pharma

Status and phase: Terminated; Phase 2

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

Treatments: Drug: Futibatinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04189445

TAS-120-202

2019-004084-49 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 115 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

115 participants in 3 patient groups

Futibatinib (Cohort A)

Experimental group

Description:

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.

Treatment:

Drug: Futibatinib

Futibatinib (Cohort B)

Experimental group

Description:

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.

Treatment:

Drug: Futibatinib

Futibatinib (Cohort C)

Experimental group

Description:

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.

Treatment:

Drug: Futibatinib