Locally Advanced Unresectable or Metastatic Solid Tumors Including Esophageal Cancer, Esophageal Adenocarcinoma, Esophageal Squamous Cell Cancer, Siewert Type 1 GEJ Cancer, Pancreatic Cancer
Conditions
Keywords
Futibatinib, Advanced esophageal cancer, Esophageal cancer, TAS-120, Immunotherapy, Esophageal squamous cell cancer (ESCC), GEJ cancer, pancreatic ductal adenocarcinoma, pancreatic cancer
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.
Interventions
DRUGIrinotecan
150 mg/m\^2 Q2W as part of mFOLFIRINOX chemotherapy.
DRUGFutibatinib
TAS-120 20 mg tablets, oral; once daily
DRUGPembrolizumab
400 mg once every 6-week-cycle, via IV infusion.
DRUGCisplatin
80 mg/m\^2 Q3W via IV infusion, as part of investigator's choice FP chemotherapy
DRUG5-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.
DRUGOxaliplatin
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.
DRUGLeucovorin
400 mg/m\^2 Q2W as part of mFOLFIRINOX or mFOLFOX6 chemotherapy.
DRUGLevoleucovorin
200 mg/m\^2 Q2W as part of investigator's choice mFOLFOX6 chemotherapy.
Sponsors
Taiho Oncology, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR by investigator assessment | 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
| Measure | Time frame | Description |
|---|---|---|
| Treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0 | 12 months | Safety will be assessed based on reported AEs (including SAEs), graded by CTCAE V5.0., and dose modifications. |
| DoR per investigator assessment | 12 months | 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 |
| DCR per investigator assessment | 12 months | defined as percentage of patients who achieve complete response, partial response or stable disease per RECIST 1.1 by investigator assessment |
| PFS per investigator assessment | 12 months | 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 |
| 6-month PFS rate | 12 months | defined as percentage of patients without disease progression within 6 months of enrollment |
Countries
France, Germany, Spain, United States
Outcome results
None listed