Nivolumab in Combination With Chemotherapy for FGFR2-positive Metastatic Gastric Cancer (NIVOFGFR2)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Gastric Cancer; FGFR2 Amplification; PD-L1 Gene Amplification
• Intervention / Treatment: Drug: Nivolumab; Drug: Capecitabine; Drug: Oxaliplatin

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 Type: Interventional
• Enrollment (Estimated): 23
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ilya Tsimafeyeu; Phone Number: +19178914943; Email: director@bucare.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Bureau for Cancer Research
      • Contact: Magnolia Rouge; Phone Number: 917-981-6485; Email: bucare@bucare.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab in combination with chemotherapy; Nivolumab 360 mg with CAPOX (capecitabine and oxaliplatin) every 3 weeks	Drug: Nivolumab; 360 mg, i.v., every 3 weeks; Other Names: Opdivo; Drug: Capecitabine; capecitabine 1000 mg/m², orally, twice a day, days 1-14 of each cycle; Other Names: Xeloda; Drug: Oxaliplatin; 130 mg/m², i.v., day 1, every 3 weeks

What is the study measuring?

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
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
Objective response rate (ORR)	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	18 months

Collaborators and Investigators

• Sponsor: Kidney Cancer Research Bureau
• Investigators: Study Chair: Ilya Tsimafeyeu, Bureau for Cancer Research

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2022
• Primary Completion (Actual): December 1, 2023
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: May 1, 2023
• First Submitted That Met QC Criteria: May 10, 2023
• First Posted (Actual): May 16, 2023

Study Record Updates

• Last Update Posted (Estimated): January 1, 2024
• Last Update Submitted That Met QC Criteria: December 26, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Capecitabine; Oxaliplatin; Nivolumab
• Other Study ID Numbers: NIVOFGFR2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No