Abstract CT124: NeoCOAST-2: a randomized, open-label, phase 2 study of neoadjuvant durvalumab plus novel immunotherapies and chemotherapy (CT) followed by adjuvant durvalumab plus novel agents, in patients with resectable non-small-cell lung cancer (NSCLC)
Authors: Cascone Tina , Spira Alexander , Campelo Rosario G. , Kim Dong-Wan , Hamid Oday , Soo-Hoo Yee , Kumar Rakesh , Grenga Italia , Forde Patrick 
Published: June 2022

Background: Neoadjuvant and adjuvant platinum-based CT improve survival rates in patients with resectable, early-stage NSCLC vs surgery alone. PD-1/PD-L1 inhibitors have shown clinical efficacy in patients with resectable, early-stage NSCLC, in both the neoadjuvant and adjuvant settings. The anti-PD-L1 monoclonal antibody (mAb) durvalumab, in combination with either the anti-CD73 mAb oleclumab or the anti-NKG2A mAb monalizumab, improved response rates and progression-free survival in patients with unresectable, Stage III NSCLC in the phase 2 COAST trial (NCT03822351). The NeoCOAST trial (NCT03794544) is currently evaluating the combination of durvalumab with oleclumab or monalizumab as neoadjuvant treatment in patients with resectable, early-stage NSCLC. NeoCOAST-2 (NCT05061550) is a multicenter study of neoadjuvant durvalumab combined with CT and either oleclumab or monalizumab, followed by surgery and adjuvant durvalumab plus oleclumab or monalizumab, in patients with resectable, Stage IIA-IIIA NSCLC.

Methods: Eligible patients must have previously untreated, histologically/cytologically confirmed NSCLC, a WHO/ECOG performance status of 0 or 1, and life expectancy of ≥12 weeks. Patients must have tumor samples available for biomarker analyses, have planned surgery consisting of lobectomy, sleeve resection, or bilobectomy, and have a pre- or post-bronchodilator FEV1 of 1.0 L and DLCO &gt;40% postoperative predictive value. Patients with sensitizing EGFR mutations or ALK translocations, history of allogeneic organ transplantation, active or prior documented autoimmune or inflammatory disorders, or uncontrolled intercurrent illness, are excluded. Approximately 140 patients will be randomized 1:1, stratified by PD-L1 expression (&lt;1% vs ≥1%), to receive IV durvalumab + oleclumab or monalizumab + CT Q3W for 4 cycles prior to surgery, followed by durvalumab + oleclumab or monalizumab Q4W post surgery. Surgery must occur within 40 days of the last dose of neoadjuvant therapy. Patients will receive adjuvant therapy starting within 10 weeks after surgery, for 12 cycles or until disease progression (per RECIST v1.1). The primary endpoints are pathological complete response rate per blinded independent pathologist review, and safety and tolerability. Secondary endpoints include investigator-assessed event-free survival and disease-free survival, feasibility of planned surgery, major pathological response rate, changes in circulating tumor DNA, investigator-assessed objective response rate following neoadjuvant therapy, overall survival, pharmacokinetics and immunogenicity.

Citation Format: Tina Cascone, Alexander Spira, Rosario G. Campelo, Dong-Wan Kim, Oday Hamid, Yee Soo-Hoo, Rakesh Kumar, Italia Grenga, Patrick Forde. NeoCOAST-2: a randomized, open-label, phase 2 study of neoadjuvant durvalumab plus novel immunotherapies and chemotherapy (CT) followed by adjuvant durvalumab plus novel agents, in patients with resectable non-small-cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT124.