CheckMate 577: A randomized, double-blind, phase 3 study of nivolumab (Nivo) or placebo in patients (Pts) with resected lower esophageal (E) or gastroesophageal junction (GEJ) cancer.

Abstract

TPS212 Background: Chemoradiotherapy (CRT) followed by surgical resection is a current standard of care (SOC) for pts with E/GEJ cancer, with 3- and 5-year survival rates ranging from 30% to 40%. Currently, no effective adjuvant SOC is available following resection. Expression of programmed death-1 (PD-1) ligands 1/2 (PD-L1/L2) has been associated with a poor prognosis in E/GEJ cancer, suggesting that PD-1 inhibition may improve outcomes. Nivo is a fully human IgG4 monoclonal antibody that targets PD-1, with demonstrated survival benefit in multiple tumor types and long-term responses in some patients. A phase 1/2 study of nivo monotherapy in chemotherapy-refractory pts with gastric/E/GEJ cancer demonstrated tumor regression, a median overall survival (OS) of 5 months, and a 12-month OS rate of 36% in pts with PD-L1+ and PD-L1- tumors (Janjigian Y, et al. J Clin Oncol. 2016;34:suppl; abstract 4010). This multinational, double-blind, phase 3 trial will evaluate nivo as an adjuvant therapy for pts with resected E/GEJ cancer (CheckMate 577; NCT02743494). Methods: In this study, an estimated 760 pts aged ≥ 18 years with stage II/III E/GEJ cancer are randomized to receive nivo or placebo. Prior to randomization, pts must have completed preoperative CRT followed by surgery and been diagnosed with residual pathological disease after being surgically rendered free of disease with negative margins following complete resection. Pts with stage 4 resectable disease, cervical esophageal cancer, or those who have not received concurrent CRT prior to surgery are not eligible for study enrollment. Primary endpoints are OS and disease-free survival. The secondary endpoint is OS rate at 1, 2, and 3 years. Clinical trial information: NCT02743494.

Emerging Multimodality Approaches to Treat Localized Esophageal Cancer

“…37 CheckMate 577 (ClinicalTrials.gov identifier: NCT02743494) is studying adjuvant nivolumab in patients with resected lower esophageal/GEJ cancer. 38 In total, 760 patients will be randomized 2:1 to either nivolumab, 240 mg intravenously every 2 weeks for 16 weeks then 480 mg every 4 weeks for a maximum of 12 months or placebo. The window for enrollment is 4 to 16 weeks postresection, and the study will complete enrollment in 2019.…”

Gastric Cancer Immunotherapy

“…В рандомизированном исследовании CheckMate-577 III фазы 760 пациентов с РЖ / КЭР получали ингибитор PD-1 ниволумаб после химиолучевой терапии и операции. Результаты исследования на данный момент не опубликованы [12].…”

Emerging Therapies in the Management of Advanced-Stage Gastric Cancer

“…The role of ICIs as adjuvant or neoadjuvant therapy in stage 2 or 3 GC is being explored in the phase III CheckMate-577 trial (Kelly et al, 2017 ). Approximately 760 patients with resected GC/GEC will be randomized to receive placebo or nivolumab (240 mg every 2 weeks) for 16 weeks, followed by nivolumab (480 mg every 4 weeks) for 1 year.…”