Testing Immunotherapy (Atezolizumab) With or Without Chemotherapy in Locoregional MSI-H/dMMR Gastric and Gastroesophageal Junction (GEJ) Cancer

Description

PRIMARY OBJECTIVE:

I. To compare three-year event-free survival (EFS) following the administration of perioperative atezolizumab and chemotherapy versus atezolizumab alone in patients with resectable microsatellite instability-high (MSI-H)/mismatch repair deficiency (dMMR) gastric and gastroesophageal junction (GEJ) cancer.

SECONDARY OBJECTIVES:

I. To assess tumor regression grade (TRG) rates following the administration of perioperative atezolizumab and chemotherapy versus atezolizumab in patients with resectable MSI-H/dMMR gastric and gastroesophageal junction (GEJ) cancer.

II. To assess overall survival (OS) following the administration of perioperative atezolizumab and chemotherapy versus atezolizumab in patients with resectable MSI-H/dMMR gastric and gastroesophageal junction (GEJ) cancer.

III. To assess the toxicity associated with the administration of perioperative atezolizumab and chemotherapy versus atezolizumab in patients with resectable MSI-H/dMMR gastric and gastroesophageal junction (GEJ) cancer.

IV. To correlate circulating tumor-derived deoxyribonucleic acid (ctDNA) clearance (defined as > 50% reduction or a reduction to undetectable levels) with TRG, EFS and OS.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A:

NEOADJUVANT THERAPY: Patients receive physician’s choice of chemotherapy regimen consisting of 4 cycles of docetaxel intravenously (IV), oxaliplatin IV, leucovorin calcium IV, and fluorouracil IV (FLOT) or 4 cycles of oxaliplatin IV, leucovorin calcium IV, and fluorouracil IV (mFOLFOX) or 3 cycles of oxaliplatin IV and capecitabine orally (PO) (CAPOX) in addition to atezolizumab IV on study.

SURGERY: Patients undergo surgery with lymphadenectomy on study.

ADJUVANT THERAPY: Patients receive FLOT, mFOLFOX, or CAPOX and atezolizumab IV as in Neoadjuvant Therapy and then receive atezolizumab IV alone.

ARM B:

NEOADJUVANT THERAPY: Patients receive 3 cycles of atezolizumab IV on study.

SURGERY: Patients undergo surgery with lymphadenectomy on study.

ADJUVANT THERAPY: Patients receive 9 cycles of atezolizumab IV on study.

All patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial. Patients may optionally undergo positron emission tomography (PET)/CT and/or collection of blood samples throughout the trial. Patients may also undergo echocardiography (ECHO) throughout the trial as clinically indicated.

Patients are followed up for 10 years from the date of randomization.