Checkmate 77T: A Phase III Trial of Neoadjuvant Nivolumab (NIVO) Plus Chemotherapy (chemo) Followed by Adjuvant Nivo in Resectable Early-Stage NSCLC.

TPS9076 Background: Although surgery for early NSCLC is potentially curative, 5-year overall survival (OS) rates for patients with stage IIA–IIIB disease are historically < 50%, representing a population of high unmet need. Conventional neoadjuvant or adjuvant chemo provides only a 5% absolute improvement in OS at 5 years. A rational approach to improve survival in these patients is to eradicate micrometastatic disease and potentially induce anti-tumor immunity to minimize the risk of relapse with peri-operative regimens including NIVO, a fully human anti–programmed death receptor-1 antibody. Early phase trials indicate that NIVO-based regimens have the potential to deepen pathological responses and extend survival in this setting (Reuss JE et al. Poster presentation at ASCO 2019. Abstract 8524; Cascone T et al. Oral presentation at ASCO 2019. Abstract 8504; Provencio M et al. Oral presentation at WCLC 2019. Abstract OA13.05). Data from the phase 2 single-arm NADIM trial (NCT03081689) demonstrated the highly encouraging major pathological response (MPR) rate of 83% with neoadjuvant NIVO plus chemo followed by adjuvant NIVO in patients with resectable stage IIIA NSCLC (Provencio M et al. Oral presentation at WCLC 2019. Abstract OA13.05). These results require validation in a large randomized controlled study. CheckMate 77T (NCT04025879) is a phase 3, randomized, double-blind trial evaluating neoadjuvant NIVO plus chemo followed by adjuvant NIVO in resectable early stage NSCLC. Methods: Approximately 452 patients aged ≥ 18 years with resectable stage IIA–IIIB (T3N2 only) NSCLC, ECOG performance status 0–1, and available lung tumor tissue will be enrolled at 113 sites in North America, South America, Europe, Asia, and Australia. Patients with EGFR/ALK mutations, brain metastasis, prior systemic anti-cancer treatment or radiotherapy, and autoimmune disease are excluded. Patients will be randomized to receive neoadjuvant NIVO plus carboplatin- or cisplatin-based doublet chemo followed by surgery and adjuvant NIVO, or neoadjuvant placebo plus carboplatin- or cisplatin-based doublet chemo followed by surgery and adjuvant placebo. The primary endpoint is event-free survival, assessed by blinded independent central review. Secondary endpoints include OS, pathological complete response and MPR assessed by blind independent pathological review, safety and tolerability. The start date was September 2019. The estimated primary completion date is May 2023. Clinical trial information: NCT04025879.