FGFR2 Amplification, Metastatic Gastric Cancer, PD-L1 Gene Amplification
Conditions
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.
Interventions
DRUGNivolumab
360 mg, i.v., every 3 weeks
DRUGCapecitabine
capecitabine 1000 mg/m², orally, twice a day, days 1-14 of each cycle
DRUGOxaliplatin
130 mg/m², i.v., day 1, every 3 weeks
Sponsors
Kidney Cancer Research Bureau
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Nivolumab in combination with chemotherapy
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1-year progression-free survival (PFS) | 12 months | Proportion of patients who will be progression-free at 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median PFS | 18 months | From first day of treatment to the first observation of disease progression or death due to any cause |
| 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 |
| 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. |
Countries
United States
Contacts
Primary ContactIlya Tsimafeyeu
Outcome results
None listed