Sequential ipilimumab (Ipi) versus best supportive care (BSC) following first-line chemotherapy (Ctx) in patients (pts) with unresectable locally advanced or metastatic gastric or gastro-esophageal junction (GEJ) cancer: A randomized, open-label, two-arm, phase II trial (CA184-162) of immunotherapy as a maintenance concept.

Abstract

TPS4151 Background: First-line systemic CTX is standard-of-care for advanced gastric cancer. However, most pts relapse or have severe adverse events (AEs), creating a need for new therapies with better benefit/risk and toxicity profiles. Endogenous immune activity against tumor cells has been demonstrated in the human gastric cancer tumor microenvironment, supporting a role for immunotherapy. As a new maintenance concept, sequential administration of immunotherapy may prolong clinical benefit of first-line CTX before disease progression (PD). Ipi, a fully human monoclonal antibody which binds CTLA-4, augments the antitumor immune response. Ipi improved overall survival (OS) in patients with advanced melanoma with AEs managed using product-specific treatment guidelines.This global (32 sites among 10 countries), multicenter, randomized, open-label, phase II trial (ClinicalTrials.gov identifier NCT01585987) will compare the efficacy of Ipi and BSC after first-line CTX. Methods: Pts with good performance status (0 or 1) and histologically confirmed, unresectable locally advanced or metastatic gastric or GEJ cancer without PD after first-line CTX with a fluoropyrimidine (F) and platinum (P) doublet will be eligible. Pts with radiological evidence of brain metastases, autoimmune/immune-mediated disease, inadequate hematologic, renal, and hepatic function, or are HER2+ will be ineligible. Pts will be randomized to Ipi (4 doses [10 mg/kg, IV Q3W], followed by Q12W) until confirmed immune-related PD or unacceptable toxicity, or to BSC (continuing F used in lead-in CTX or no active systemic therapy). The primary objective is to compare immune-related progression-free survival (PFS): immune-related response criteria were derived from World Health Organization (WHO) criteria to better capture Ipi response patterns. Secondary objectives are to compare PFS per mWHO criteria and OS, and estimate immune-related best overall response rate. The study is planned to randomize 114 pts. Clinical trial information: NCT01585987.