Phase 2 Futibatinib in Combination With PD-1 Antibody Based Standard of Care in Solid Tumors

Study Overview
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Brief Summary
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This is a nonrandomized, uncontrolled, open-label, multicenter Phase 2 study to evaluate the efficacy, safety, and tolerability of futibatinib in combination with PD-1 antibody-based SoC therapy in adult patients with solid tumors.

Detailed Description
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Patients with locally advanced, unresectable or metastatic esophageal cancer (EC) will receive futibatinib in combination with pembrolizumab plus Investigator choice of chemotherapy (FP or mFOLFOX6). The study will begin with a safety lead-in period (Part 1), in which approximately 12 patients with advanced or metastatic esophageal cancer will be enrolled. In Part 2, approximately 14 EC patients will be enrolled and treated with the same treatment regimen.

Official Title
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A Phase 2 Study of Futibatinib in Combination With PD-1 Antibody-based Standard of Care Therapy in Patients With Solid Tumors.

Conditions
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Locally Advanced Unresectable or Metastatic Esophageal Cancer

Intervention / Treatment
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* Drug: Futibatinib
* Drug: Pembrolizumab
* Drug: Cisplatin
* Drug: 5-FU
* Drug: Oxaliplatin
* Drug: Leucovorin
* Drug: Levoleucovorin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is ≥18 years of age at the time of informed consent Histologically or cytologically confirmed, locally advanced, unresectable or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the esophagogastric junction (EGJ). No prior systemic treatment for locally advanced, unresectable or metastatic esophageal carcinoma. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Have documentation of PD-L1 CPS score. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Adequate organ function Able to take medications orally Exclusion Criteria: Has locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy (as determined by local investigator). Has an adenocarcinoma histology and is eligible to receive approved targeted therapy (eg, HER-2 positive patients). Has received prior treatment with an anti-PD-1/PD-L1 or FGF/FGFR targeting drug, or any other agent directed to stimulatory or co-stimulatory T-cell receptor. Has known additional malignancy that is progressing or requires active treatment . History or current evidence of calcium and phosphate homeostasis disorder Current evidence of clinically significant retinal disorder Pregnant or lactating female. Has known hypersensitivity or severe reaction to any of the study drugs or their excipients. Has a diagnosis of immunodeficiency. Has known human immunodeficiency virus (HIV) and/or history of Hepatitis B or C infections, or known to be positive for Hepatitis B antigen (HBsAg)/ Hepatitis B virus (HBV) DNA or Hepatitis C antibody or RNA. Has an active autoimmune disease that has required systemic treatment in the past 2 years Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis. Has had an allogenic tissue/organ transplant.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: futibatinib + pembrolizumab + chemotherapy<br>Futibatinib will be administered once daily on a continuous dosing regimen in combination with pembrolizumab plus investigator choice of SoC chemotherapy of FP or mFOLFOX6 induction phase followed by a Futibatinib Plus Pembrolizumab consolidation phase. | Drug: Futibatinib<br>* TAS-120 20 mg tablets, oral; once daily<br>* Other names: TAS-120;Drug: Pembrolizumab<br>* 400 mg once every 6-week-cycle, via IV infusion.<br>* Other names: KEYTRUDA®;Drug: Cisplatin<br>* 80 mg/m^2 Q3W via IV infusion, as part of investigator's choice FP chemotherapy<br>* Other names: PLATINOL®;Drug: 5-FU<br>* 4000 mg/m^2 Q3W via IV infusion, as part of investigator's choice FP chemotherapy or 400 mg/m^2 Q2W via bolus IV infusion followed by 2400 mg/m^2 Q2W via continuous IV infusion, as part of investigator's choice mFOLFOX6 chemotherapy<br>* Other names: ADRUCIL®;Drug: Oxaliplatin<br>* 85 mg/m^2 Q2W via IV infusion, as part of investigator's choice mFOLFOX6 chemotherapy.<br>* Other names: ELOXATIN®;Drug: Leucovorin<br>* 400 mg/m^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy<br>* Other names: WELLCOVORIN®;Drug: Levoleucovorin<br>* 200 mg/m^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy.<br>* Other names: FUSILEV®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR by investigator assessment | 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 | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0 | Safety will be assessed based on reported AEs (including SAEs), graded by CTCAE V5.0., and dose modifications. | 12 months | 
| DoR per investigator assessment | defined as time from the first documentation of response to the first documentation of objective tumor progression or death due to any cause, whichever occurs first | 12 months | 
| DCR per investigator assessment | defined as percentage of patients who achieve complete response, partial response or stable disease per RECIST 1.1 by investigator assessment | 12 months | 
| PFS per investigator assessment | defined as the time from date of enrollment to the date of disease progression based on Investigator assessment of radiographic images or death, whichever occurs first | 12 months | 
| 6-month PFS rate | defined as percentage of patients without disease progression within 6 months of enrollment | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Futibatinib, Advanced esophageal cancer, Esophageal cancer, TAS-120, Immunotherapy, Esophageal squamous cell cancer (ESCC), GEJ cancer