Perioperative Treatment in Resectable Gastric Cancer With Spartalizumab (PDR001) in Combination With Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel (FLOT)

Study Overview
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Brief Summary
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Multicenter, open-label, non randomized, phase 2 trial in resectable gastric or gastroesophageal junction adenocarcinoma: Perioperative Treatment by Spartalizumab (PDR001) in Combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT)

Official Title
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Perioperative Treatment in Resectable Gastric Cancer With Spartalizumab (PDR001) in Combination With Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel (FLOT): A Phase II Study (GASPAR)

Conditions
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Gastric Cancer by AJCC V8 Stage, Resectable Carcinoma

Intervention / Treatment
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* Drug: perioperative treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Untreated localized gastric or GEJ adenocarcinoma considered resectable (clinical stage ≥cT2 and/or cN+ and no metastasis) Histologically confirmed adenocarcinoma ECOG performance status score of 0 or 1 Tumor tissue must be provided for biomarker analyses (fresh or archival with an FFPE tissue block) All subjects must consent to allow the acquisition of blood samples for performance of correlative studies Screening laboratory values must meet the following criteria: WBC ≥ 2000/ mm³ Neutrophils ≥ 1500/ mm³ Platelets ≥ 100 000/ mm³ Hemoglobin ≥ 9.0 g/dL Bilirubin ≤ 1.5 x ULN, AST and ALT ≤ 3 x ULN Measured or calculated creatinine ≥ 50 ml/min clearance (CrCl) (using the Cockcroft-Gault formula) Potassium ≥ LLN Magnesium ≥ LLN Calcium ≥ LLN Female subject of childbearing potential must have a negative urine or serum pregnancy test within 72h before study start Subject in reproductive age must be willing to use adequate contraception during the study and at least 9 months in men and 12 months in women after the last dose of investigational drug. In addition, given the toxicities observed on the male reproductive system, a conservation of gametes will be proposed for men, as usually in routine practice Subject affiliated to a social security regimen Patient has signed informed consents obtained before any trial related activities and according to local guidelines Exclusion Criteria: Subject with any distant metastasis Subject with no recovering from the effects of major surgery or significant traumatic injury within 14 days before inclusion Documented significant cardiovascular disease within the past 6 months before the first dose of study treatment, including: history of congestive heart failure (defined as NYHA III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis History of anterior organ transplant, including stem cell allograft Pneumonitis or interstitial lung disease History of other malignancy within the previous 3 years (except for appropriately treated in-situ cervix carcinoma and non-melanoma skin carcinoma) Subject with active, known, or suspected autoimmune disease Subject with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment GASPAR Protocol - EUDRACT number: 2020-004497-21 - version 1.3 / 2021-01-18 Page 8 sur 44 Known history of HIV or HBV infection Known active HCV infection Known history of active tuberculosis Vaccination with live vaccine within 30 days before the first dose of study treatment Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Recent or concomitant treatment with brivudine (herpes virostatic) Prior anticancer therapy for the current malignancy Known hypersensitivity to any of the study drugs or their excipients Chronic inflammable gastro-intestinal disease Uracilemia ≥ 16 ng/ml QT/QTc > 450 msec for men and > 470 msec for women Peripheral neuropathy ≥ Grade II Uncontrolled diabetes Active infection requiring systemic therapy Participation in another therapeutic clinical study Patient deprived of liberty or placed under the authority of a tutor Patient assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FLOT regimen plus Spartalizumab<br>Standard FLOT regimen Docetaxel 50 mg/m² IV infusion on D1 Oxaliplatine 85 mg/m² IV infusion on D1 Leucovorin 200 mg/m² IV infusion on D1 Fluorouracile 2600 mg/m² 24 h IV infusion on D1 with Spartalizumab PDR001 Patients will received the fixed dose of 400 mg per IV infusion on D1 every four weeks (q4w) for 2 pre-operative cycles (8 weeks) and 2 post-operative cycles (8 weeks) | Drug: perioperative treatment<br>* FLOT + Spartalizumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic response after pre-operative treatment | Proportion of patients with pCR (pathologic complete response) in the primary tumour defined as: no tumour residue found in the tissue collected during the surgery evaluated by the pathologist | At surgery, an average 3 months after treatment initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the impact of perioperative treatment on disease-free survival | Disease-free survival (DFS) defined as time between inclusion and first disease progression | Through study completion, an average of 5 follow-up year | 
| Evaluate the impact of perioperative treatment on overall survival | Overall survival (OS) defined as the time between inclusion and death whatever cause; | Up to death | 
| The correlation between pathologic Complete response and survival outcomes (disease-free and overall survival) | Proportion of patients with margin-free resection (R0), defined as a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed | At surgery, an average 3 months after treatment initiation | 
| Treatment-Related Adverse Events | Type, grade and number of Adverse Events as Assessed by CTCAE v5.0 | Toxicities occurring up to 1 month after the end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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perioperative, spartalizumab, PDR001, Gastric Cancer