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.

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.

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.