Neoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase 2 NeoCOAST Platform Trial

Tina Cascone, Gozde Kar, Jonathan D. Spicer, Rosario Garcia-Campelo, Walter Weder, Davey B. Daniel, David R. Spigel, Maen Hussein, Julien Mazieres, Julio Oliveira, Edwin H. Yau, Alexander I. Spira, Valsamo Anagnostou, Raymond Mager, Oday Hamid, Lin-Yang Cheng, Ying Zheng, Jorge Blando, Tze Heng Tan, Michael Surace, Jaime Rodriguez-Canales, Vancheswaran Gopalakrishnan, Bret R. Sellman, Italia Grenga, Yee Soo-Hoo, Rakesh Kumar, Lara McGrath, Patrick M. Forde

Neoadjuvant chemo-immunotherapy improves pathological complete response rate and event-free survival in patients with resectable non-small-cell lung cancer (NSCLC), versus chemotherapy alone. NeoCOAST was the first randomized, multi-drug, platform trial to examine novel neoadjuvant immuno-oncology combinations for patients with resectable NSCLC, using major pathological response (MPR) as the primary endpoint. Eighty-three patients received a single cycle of treatment: 26 received durvalumab (anti-PD-L1) monotherapy, 21 received durvalumab plus oleclumab (anti-CD73), 20 received durvalumab plus monalizumab (anti-NKG2A), and 16 received durvalumab plus danvatirsen (anti-STAT3 antisense oligonucleotide). MPR rates were higher for patients in the combination arms, versus durvalumab alone. Safety profiles for the combinations were similar to that of durvalumab alone. Multiplatform immune profiling suggested improved MPR rates in the durvalumab plus oleclumab and durvalumab plus monalizumab arms were associated with enhanced effector immune infiltration of tumors, interferon responses and markers of tertiary lymphoid structure formation, and systemic functional immune-cell activation.