Checkmate 816: A phase 3, randomized, open-label trial of nivolumab plus ipilimumab vs platinum-doublet chemotherapy as neoadjuvant treatment for early-stage NSCLC.

Abstract

TPS8577 Background: At initial diagnosis, 20% of patients (pts) with NSCLC present with early-stage disease. The 5-year overall survival (OS) rate after surgery for stage IB–IIIA NSCLC is 25%–60%. Addition of adjuvant chemotherapy to surgery only provides a 5% absolute OS benefit at 5 years. Neoadjuvant treatment with immune checkpoint inhibitors may extend OS in early-stage NSCLC by enhancing systemic immunity and eradicating micrometastatic disease. In contrast to the adjuvant setting, the neoadjuvant setting is associated with a higher tumor burden, the presence of abundant tumor antigens, and the consequent potential for tumor-associated neoantigen presentation to the immune system. In an ongoing feasibility trial in pts with stage IB–IIIA NSCLC, nivolumab (nivo; a fully human PD-1 immune checkpoint inhibitor antibody) given alone as neoadjuvant treatment induced a major pathological response (MPR; < 10% residual viable tumor cells) rate of 39% (7/18), did not delay or interfere with surgery, and was not associated with new safety signals. In a phase 1 study in pts with stage IIIB/IV NSCLC, first-line nivo + ipilimumab (ipi; a CTLA-4 immune checkpoint inhibitor antibody) showed a greater radiologic objective response rate than nivo alone (39% vs 23%). These data provided the rationale for Checkmate 816 (NCT02998528), a phase 3 study evaluating nivo + ipi vs platinum-doublet chemotherapy as neoadjuvant treatment for early-stage NSCLC. Methods: Approximately 326 pts aged ≥18 years with resectable stage IB/II/IIIA NSCLC, ECOG performance status 0–1, pulmonary function capable of tolerating lung resection, and available lung tumor tissue will be enrolled in North America, South America, Europe, and Asia. Pts are ineligible if they have autoimmune disease or had received prior treatment with immune checkpoint inhibitors. Pts will be randomized to receive nivo + ipi or platinum-doublet chemotherapy. The primary endpoint is MPR rate. Secondary endpoints include event-free survival, OS, and complete pathological response. Start date is January 2017. The estimated primary completion date is July 2019. Clinical trial information: NCT02998528.