Clinical trial NCT05859477: Nivolumab in Combination With Chemotherapy for FGFR2-positive Metastatic Gastric Cancer
Official title: Nivolumab and CAPOX in Patients With FGFR2/PD-L1-positive Metastatic Gastric Adenocarcinoma: a Single-arm, Phase 2 Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Gastric Cancer
PD-L1 Gene Amplification
FGFR2 Amplification
Lead sponsor: Kidney Cancer Research Bureau
Sponsor class: OTHER
First posted: 2023-05-16
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Nivolumab in combination with chemotherapy
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 1-year progression-free survival (PFS)
timeFrame: 12 months
Secondary outcomes:
measure: Median PFS
timeFrame: 18 months
measure: Median overall survival (OS)
timeFrame: 24 months
measure: Objective response rate (ORR)
timeFrame: 18 months
measure: Toxicity Summary
timeFrame: Up to 30 days post treatment
Other outcomes:
Locations:
city: New York
country: United States
facility: Bureau for Cancer Research
state: New York
Study officials:
affiliation: Bureau for Cancer Research
name: Ilya Tsimafeyeu
role: STUDY_CHAIR
References: