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

Sponsor

Taiho Oncology, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05945823

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced Unresectable or Metastatic Esophageal Cancer	Drug: Futibatinib Drug: Pembrolizumab Drug: Cisplatin Drug: 5-FU Drug: Oxaliplatin Drug: Leucovorin Drug: Levoleucovorin	Phase 2

Detailed Description

Patients with locally advanced, unresectable or metastatic esophageal cancer (EC) will receive futibatinib in combination with pembrolizumab plus Investigator choice of chemotherapy (FP or mFOLFOX6). The study will begin with a safety lead-in period (Part 1), in which approximately 12 patients with advanced or metastatic esophageal cancer will be enrolled. In Part 2, approximately 14 EC patients will be enrolled and treated with the same treatment regimen.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

26 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

May 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: futibatinib + pembrolizumab + chemotherapy Futibatinib will be administered once daily on a continuous dosing regimen in combination with pembrolizumab plus investigator choice of SoC chemotherapy of FP or mFOLFOX6 induction phase followed by a Futibatinib Plus 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 Other Names: ADRUCIL® Drug: Oxaliplatin 85 mg/m^2 Q2W via IV infusion, as part of investigator's choice mFOLFOX6 chemotherapy. Other Names: ELOXATIN® Drug: Leucovorin 400 mg/m^2 Q2W as part of investigator's choice 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®

Arm

Intervention/Treatment

Experimental: futibatinib + pembrolizumab + chemotherapy

Futibatinib will be administered once daily on a continuous dosing regimen in combination with pembrolizumab plus investigator choice of SoC chemotherapy of FP or mFOLFOX6 induction phase followed by a Futibatinib Plus 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

Other Names:

ADRUCIL®

Drug: Oxaliplatin

85 mg/m^2 Q2W via IV infusion, as part of investigator's choice mFOLFOX6 chemotherapy.

Other Names:

ELOXATIN®

Drug: Leucovorin

400 mg/m^2 Q2W as part of investigator's choice 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®

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Is ≥18 years of age at the time of informed consent
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).
No prior systemic treatment for locally advanced, unresectable or metastatic esophageal carcinoma.
Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines.
Have documentation of PD-L1 CPS score.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Adequate organ function
Able to take medications orally

Exclusion Criteria:

Has locally advanced esophageal carcinoma 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.
Has an active autoimmune disease that has required systemic treatment in the past 2 years
Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
Has had an allogenic tissue/organ transplant.