Vanderbilt Clinical Trials

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

Purpose

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.

Conditions

Locally Advanced Unresectable or Metastatic Solid Tumors Including Esophageal Cancer
Esophageal Adenocarcinoma
Esophageal Squamous Cell Cancer
Siewert Type 1 GEJ Cancer
Pancreatic Cancer

Eligibility

Eligible Ages: Over 18 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

Inclusion Criteria

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

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 Design

Phase: Phase 2
Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
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: Futibatinib TAS-120 20 mg tablets, oral; once daily Other names: TAS-120 Drug: Pembrolizumab 400 mg once every 6-week-cycle, via IV infusion. Other names: MK-3475 KEYTRUDA® 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: 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® Drug: Leucovorin 400 mg/m^2 Q2W as part of mFOLFIRINOX or mFOLFOX6 chemotherapy. Other names: calcium folinate folinic acid WELLCOVORIN® Drug: Levoleucovorin 200 mg/m^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy. Other names: calcium levofolinate levofolinic acid FUSILEV®
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: Futibatinib TAS-120 20 mg tablets, oral; once daily Other names: TAS-120 Drug: Pembrolizumab 400 mg once every 6-week-cycle, via IV infusion. Other names: MK-3475 KEYTRUDA® 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: 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® Drug: Leucovorin 400 mg/m^2 Q2W as part of mFOLFIRINOX or mFOLFOX6 chemotherapy. Other names: calcium folinate folinic acid WELLCOVORIN® Drug: Levoleucovorin 200 mg/m^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy. Other names: calcium levofolinate levofolinic acid FUSILEV® Drug: Irinotecan 150 mg/m^2 Q2W as part of mFOLFIRINOX chemotherapy.

Recruiting Locations

Vanderbilt University Medical Center
Nashville, Tennessee 37232

Contact:
615-875-3417
mike.gibson.1@vumc.org

More Details

Status: Recruiting
Sponsor: Taiho Oncology, Inc.

Study Contact

Taiho Oncology, Inc
+1 844-878-2446
medicalinformation@taihooncology.com

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.