Nivolumab in Combination With Chemotherapy for FGFR2-positive Metastatic Gastric Cancer

Phase 2

Recruiting

• Conditions: PD-L1 Gene Amplification; FGFR2 Amplification; Metastatic Gastric Cancer
• Interventions: Drug: Nivolumab; Drug: Capecitabine; Drug: Oxaliplatin

• Registration Number: NCT05859477
• Lead Sponsor: Kidney Cancer Research Bureau

Brief Summary

The goal of this phase 2 clinical trial is to evaluate the efficacy of nivolumab in combination with CAPOX in patients with FGFR2-positive/PD-L1-positive/HER2-negative metastatic gastric cancer.

Detailed Description

On April 16, 2021, the Food and Drug Administration approved first-line therapy with nivolumab and fluoropyrimidine-platinum-containing chemotherapy for metastatic gastric adenocarcinoma. Patients with PD-L1 expression benefit the most from this treatment.

Fibroblast growth factor receptor 2 (FGFR2) is a predictor of poor overall survival and a potential target for targeted therapy. However, there is no data of nivolumab efficacy in patients with combined expression of PD-L1 and FGFR2.

The aim of this study is to evaluate the preliminary efficacy of nivolumab in this patient population.

Study Timeline

• Study Start: 2022-06-05
• Study First Submitted: 2023-05-01
• Study First Submitted QC: 2023-05-10
• Study First Posted: 2023-05-16
• Status Verified: 2023-12
• Primary Completion: 2023-12-01
• Last Update Submitted: 2023-12-26
• Last Update Posted: 2024-01-02
• Study Completion: 2024-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

• Previously untreated, unresectable advanced or metastatic gastric adenocarcinoma
• Measurable lesions according to the RECIST 1.1 criteria
• PD-L1 Combined Positive Score (CPS) of five or more assessed by Dako PD-L1 immunohistochemistry 28-8 pharmDx assay
• Positive FGFR2 overexpression status by immunohistochemistry defined as exhibiting any moderate (2+) to strong (3+) membranous staining in more than 1% of tumor cells
• Possibility to assess the amplification of FGFR2
• HER2-negative status
• ECOG PS 0-2
• Age >= 18 years old
• Adequate function of organs
• Absence of any psychological, family, social or geographical circumstances that could potentially serve as obstacles to the implementation of the study
• Signed Informed Consent

Exclusion Criteria

• Participation in another clinical study and concomitant treatment with any research drug or any study of antitumor therapy, including radiation, within 28 days before inclusion in this study
• Presence of metastases in the central nervous system and / or carcinoma of the meninges at the time of inclusion in the study
• Presence or history of present signs of any condition, therapy or laboratory abnormalities that could limit the interpretation of the results of this study
• Any malignant tumor within the previous 5 years, with the exception of adequately cured cervical cancer in situ or squamous cell skin cancer, or basal cell skin cancer with limited growth, subject to adequate control over the course of this disease
• Pregnancy
• Known positive status for human immunodeficiency virus (HIV) or active hapatitis B and C
• Surgery within 7 days before the first dose of the study drug
• Signs of bleeding or hemorrhagic diathesis

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nivolumab in combination with chemotherapy	Nivolumab	Nivolumab 360 mg with CAPOX (capecitabine and oxaliplatin) every 3 weeks
Nivolumab in combination with chemotherapy	Oxaliplatin	Nivolumab 360 mg with CAPOX (capecitabine and oxaliplatin) every 3 weeks
Nivolumab in combination with chemotherapy	Capecitabine	Nivolumab 360 mg with CAPOX (capecitabine and oxaliplatin) every 3 weeks

Primary Outcome Measures

Name	Time	Method
1-year progression-free survival (PFS)	12 months	Proportion of patients who will be progression-free at 1 year

Secondary Outcome Measures

Name	Time	Method
Median PFS	18 months	From first day of treatment to the first observation of disease progression or death due to any cause
Toxicity Summary	Up to 30 days post treatment	toxicity assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 3 and above adverse events possibly, probably or definitely related to treatment.
Median overall survival (OS)	24 months	From first day of treatment to time of death due to any cause.
Objective response rate (ORR)	18 months	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Trial Locations

Locations (1)

Bureau for Cancer Research; 🇺🇸 New York, New York, United States