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

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)


Eligibility Criteria:
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