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

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

Detailed Description
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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.

Official Title
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Nivolumab and CapeOX in Patients With FGFR2/PD-L1-positive Metastatic Gastric Adenocarcinoma: a Single-arm, Phase 2 Study

Conditions
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Metastatic Gastric Cancer, PD-L1 Gene Amplification, FGFR2 Amplification

Intervention / Treatment
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* Drug: Nivolumab
* Drug: Capecitabine
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Nivolumab in combination with chemotherapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab in combination with chemotherapy<br>Nivolumab 360 mg with CapeOX (capecitabine and oxaliplatin) every 3 weeks | Drug: Nivolumab<br>* 360 mg, i.v., every 3 weeks<br>* Other names: Opdivo;Drug: Capecitabine<br>* capecitabine 1000 mg/m², orally, twice a day, days 1-14 of each cycle<br>* Other names: Xeloda;Drug: Oxaliplatin<br>* 30 mg/m², i.v., day 1, every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year progression-free survival (PFS) | Proportion of patients who will be progression-free at 1 year | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median PFS | From first day of treatment to the first observation of disease progression or death due to any cause | 18 months | 
| Median overall survival (OS) | From first day of treatment to time of death due to any cause. | 24 months | 
| Objective response rate (ORR) | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) 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 | 18 months | 
| Toxicity Summary | 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. | Up to 30 days post treatment |