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

Authors

Tina Cascone
Gozde Kar
Jonathan D Spicer
Rosario García-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

Publication Date

11-1-2023

Journal

Cancer Discvoery

Abstract

Neoadjuvant chemoimmunotherapy improves pathologic 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, multidrug platform trial to examine novel neoadjuvant immuno-oncology combinations for patients with resectable NSCLC, using major pathologic response (MPR) rate 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 those of durvalumab alone. Multiplatform immune profiling suggested that 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.

Significance: A neoadjuvant platform trial can rapidly generate clinical and translational data using candidate surrogate endpoints like MPR. In NeoCOAST, patients with resectable NSCLC had improved MPR rates after durvalumab plus oleclumab or monalizumab versus durvalumab alone and tumoral transcriptomic signatures indicative of augmented immune cell activation and function. See related commentary by Cooper and Yu, p. 2306. This article is featured in Selected Articles from This Issue, p. 2293.

Keywords

Humans, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Neoadjuvant Therapy

Comments

Trial registration: ClinicalTrials.gov NCT03794544.

See editorial "Dual immuno-oncology agents as neoadjuvant therapy for patients with resectable non-small cell lung cancer" in Transl Lung Cancer Res, volume 13 on page 229. See editorial "Novel immunotherapy combinations in neoadjuvant non-small cell lung cancer (NSCLC): a better chance at cure?" in Transl Lung Cancer Res, volume 13 on page 673. Supplementary Materials
PMID: 37707791