A Phase 2 Study of Futibatinib in Combination With PD-1 Antibody-based Standard of Care Therapy in Patients With Solid Tumors.
Overview
- Phase
- Phase 2
- Intervention
- 5-FU
- Conditions
- Locally Advanced Unresectable or Metastatic Solid Tumors Including Esophageal Cancer
- Sponsor
- Taiho Oncology, Inc.
- Enrollment
- 53
- Locations
- 44
- Primary Endpoint
- ORR by investigator assessment
- Status
- Active, not recruiting
- Last Updated
- 23 days ago
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Is ≥18 years of age at the time of informed consent
- •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).
- •Cohort B: Histologically or cytologically confirmed, locally advanced, unresectable or metastatic pancreatic ductal adenocarcinoma.
- •No prior systemic treatment for locally advanced, unresectable or metastatic disease
- •Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Adequate organ function
- •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).
- •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.
Arms & Interventions
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).
Intervention: 5-FU
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).
Intervention: Futibatinib
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).
Intervention: Pembrolizumab
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).
Intervention: Cisplatin
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).
Intervention: Oxaliplatin
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).
Intervention: Leucovorin
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) .
Intervention: Futibatinib
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).
Intervention: Levoleucovorin
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) .
Intervention: 5-FU
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) .
Intervention: Pembrolizumab
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) .
Intervention: Oxaliplatin
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) .
Intervention: Leucovorin
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) .
Intervention: Irinotecan
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) .
Intervention: Levoleucovorin
Outcomes
Primary Outcomes
ORR by investigator assessment
Time Frame: 12 months
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
Secondary Outcomes
- Treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0(12 months)
- DoR per investigator assessment(12 months)
- DCR per investigator assessment(12 months)
- PFS per investigator assessment(12 months)
- 6-month PFS rate(12 months)