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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreatic Cancer; Esophageal Adenocarcinoma; Esophageal Squamous Cell Cancer; Locally Advanced Unresectable or Metastatic Solid Tumors Including Esophageal Cancer; Siewert Type 1 GEJ Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Levoleucovorin; Drug: Futibatinib; Drug: Cisplatin; Drug: 5-FU; Drug: Leucovorin; Drug: Irinotecan; Drug: Oxaliplatin

Detailed Description

Patients with locally advanced, unresectable or metastatic esophageal cancer (EC) or pancreatic ductal adenocarcinoma (PDAC) will receive futibatinib in combination with pembrolizumab plus standard of care (SOC) chemotherapy. Patients with EC will receive Investigator choice of chemotherapy (FP or mFOLFOX6), patients with PDAC will receive mFOLFIRINOX. Subjects will receive futibatinib in combination with pembrolizumab plus standard of care (SOC) chemotherapy during induction phase of the study and will continue on futibatinib in combination with pembrolizumab in consolidation phase.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Expanded Access

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Contacts and Locations

Study Locations

• France
  • Lille, France, 59037
    • Centre Hospitalier Regional Universitaire de Lille
  • Poitiers, France, 86000
    • Centre Hospitalier Regional Universitaire Poitiers
• Germany
  • Frankfurt, Germany, 60488
    • Krankenhaus Nordwest gGmbH
  • Mainz, Germany, 55131
    • Universitaetsmedizin Mainz
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
• United States
  • California
    • Santa Monica, California, United States, 90404
      • University of California Los Angeles UCLA - Cancer Care - Santa Monica
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers Midtown
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Comprehensive Cancer Center
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center and Research Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • New Jersey
    • Mickleton, New Jersey, United States, 08056
      • The Minniti Center - Medical Oncology and Hematology
  • New York
    • Buffalo, New York, United States, 14203
      • Roswell Park Comprehensive Cancer Center (RPCCC) (Roswell Park Cancer Institute (RPCI))
    • New York, New York, United States, 10016
      • NYU Langone
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Research LLC
  • Pennsylvania
    • Horsham, Pennsylvania, United States, 19044
      • Alliance Cancer Specialists
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75216
      • Dallas VA Medical Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute
    • Roanoke, Virginia, United States, 24014
      • Blue Ridge Cancer Care
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

1. Is ≥18 years of age at the time of informed consent
2. Cohort A: 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).
3. Cohort B: Histologically or cytologically confirmed, locally advanced, unresectable or metastatic pancreatic ductal adenocarcinoma.
4. No prior systemic treatment for locally advanced, unresectable or metastatic disease
5. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
7. Adequate organ function
8. Able to take medications orally

Exclusion Criteria

1. Has locally advanced disease that is resectable or potentially curable with radiation therapy (as determined by local investigator).
2. Has an adenocarcinoma histology and is eligible to receive approved targeted therapy (eg, HER-2 positive patients).
3. 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.
4. Has known additional malignancy that is progressing or requires active treatment.
5. History or current evidence of calcium and phosphate homeostasis disorder
6. Current evidence of clinically significant retinal disorder
7. Pregnant or lactating female.
8. Has known hypersensitivity or severe reaction to any of the study drugs or their excipients.
9. Has a diagnosis of immunodeficiency.
10. 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.
11. Has an active autoimmune disease that has required systemic treatment in the past 2 years
12. Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
13. Has had an allogenic tissue/organ transplant.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; Patients with Esophageal cancer (Adenocarcinoma or Squamous cell cancer) will receive Futibatinib administered once daily on a continuous dosing regimen in combination with pembrolizumab plus investigator choice of SoC chemotherapy (FP or mFOLFOX6) for 6 cycles (induction phase) following by Futibatinib combination with pembrolizumab (consolidation phase).	Drug: Pembrolizumab; 400 mg once every 6-week-cycle, via IV infusion.; Other Names: MK-3475; KEYTRUDA®; Drug: Levoleucovorin; 200 mg/m^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy.; Other Names: FUSILEV®; calcium levofolinate; levofolinic acid; Drug: Futibatinib; TAS-120 20 mg tablets, oral; once daily; Other Names: TAS-120; Drug: Cisplatin; 80 mg/m^2 Q3W via IV infusion, as part of investigator's choice FP chemotherapy; Other Names: PLATINOL®; Drug: 5-FU; 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. 2400 mg/m^2 Q2W via continuous IV infusion, as part of investigator's choice mFOLFOX6 chemotherapy. 2400 mg/m^2 Q2W via continuous IV infusion, as part of mFOLFIRINOX chemotherapy.; Other Names: ADRUCIL®; Drug: Leucovorin; 400 mg/m^2 Q2W as part of mFOLFIRINOX or mFOLFOX6 chemotherapy.; Other Names: folinic acid; WELLCOVORIN®; calcium folinate; Drug: Oxaliplatin; 85 mg/m^2 Q2W via IV infusion, as part of mFOLFIRINOX or mFOLFOX6 chemotherapy. 2400 mg/m^2 Q2W via continuous IV infusion, as part of mFOLFIRINOX chemotherapy.; Other Names: ELOXATIN®
Experimental: Cohort B; Patients with PDAC will receive Futibatinib administered once daily on a continuous dosing regimen in combination with pembrolizumab plus mFOLFIRINOX for 6 cycles (induction phase) following by Futibatinib combination with pembrolizumab (consolidation phase) .	Drug: Pembrolizumab; 400 mg once every 6-week-cycle, via IV infusion.; Other Names: MK-3475; KEYTRUDA®; Drug: Levoleucovorin; 200 mg/m^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy.; Other Names: FUSILEV®; calcium levofolinate; levofolinic acid; Drug: Futibatinib; TAS-120 20 mg tablets, oral; once daily; Other Names: TAS-120; Drug: 5-FU; 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. 2400 mg/m^2 Q2W via continuous IV infusion, as part of investigator's choice mFOLFOX6 chemotherapy. 2400 mg/m^2 Q2W via continuous IV infusion, as part of mFOLFIRINOX chemotherapy.; Other Names: ADRUCIL®; Drug: Leucovorin; 400 mg/m^2 Q2W as part of mFOLFIRINOX or mFOLFOX6 chemotherapy.; Other Names: folinic acid; WELLCOVORIN®; calcium folinate; Drug: Irinotecan; 150 mg/m^2 Q2W as part of mFOLFIRINOX chemotherapy.; Drug: Oxaliplatin; 85 mg/m^2 Q2W via IV infusion, as part of mFOLFIRINOX or mFOLFOX6 chemotherapy. 2400 mg/m^2 Q2W via continuous IV infusion, as part of mFOLFIRINOX chemotherapy.; Other Names: ELOXATIN®

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Taiho Oncology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2023
• Primary Completion (Actual): January 28, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: July 6, 2023
• First Submitted That Met QC Criteria: July 6, 2023
• First Posted (Actual): July 14, 2023

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; pancreatic cancer; GEJ cancer; Esophageal cancer; pancreatic ductal adenocarcinoma; Futibatinib; TAS-120; Advanced esophageal cancer; Esophageal squamous cell cancer (ESCC)
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Pancreatic Diseases; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Esophageal Neoplasms; Pancreatic Neoplasms; Adenocarcinoma Of Esophagus; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Camptothecin; Alkaloids; Enzymes and Coenzymes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Platinum Compounds; Oxaliplatin; Irinotecan; Fluorouracil; Leucovorin; Levoleucovorin; Cisplatin; pembrolizumab; futibatinib
• Other Study ID Numbers: TAS-120-206

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No