Updated results from COAST, a phase 2 study of durvalumab (D) ± oleclumab (O) or monalizumab (M) in patients (pts) with stage III unresectable non-small cell lung cancer (uNSCLC).

Charu Aggarwal Penn Medicine Abramson Cancer Center, Philadelphia, PA info_outline Charu Aggarwal, Alex Martinez-Marti, Margarita Majem, Fabrice Barlesi, Enric Carcereny, Quincy S. Chu, Isabelle Monnet, Alfredo Sanchez, Shaker R. Dakhil, David Ross Camidge, Marine Pillet, Miranda Brown, Adam Dowson, Zachary A. Cooper, Rakesh Kumar, Roy S. Herbst

Authors Charu Aggarwal Penn Medicine Abramson Cancer Center, Philadelphia, PA info_outline Charu Aggarwal, Alex Martinez-Marti, Margarita Majem, Fabrice Barlesi, Enric Carcereny, Quincy S. Chu, Isabelle Monnet, Alfredo Sanchez, Shaker R. Dakhil, David Ross Camidge, Marine Pillet, Miranda Brown, Adam Dowson, Zachary A. Cooper, Rakesh Kumar, Roy S. Herbst Organizations Penn Medicine Abramson Cancer Center, Philadelphia, PA, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Barcelona, Spain, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, Gustave Roussy and Paris Saclay University, Villejuif, France, Institut Català d'Oncologia, Badalona-Hospital Germans Trias i Pujol, Badalona, Spain, Cross Cancer Institute, Edmonton, AB, Canada, Centre Hospitalier Intercommunal de Créteil, Créteil, France, Consorcio Hospitalario Provincial de Castellón, Castellón, Spain, Cancer Center of Kansas, Wichita, KS, University of Colorado Anschutz Medical Center, Aurora, CO, AstraZeneca, Cambridge, United Kingdom, AstraZeneca, Gaithersburg, MD, Yale Cancer Center, New Haven, CT Abstract Disclosures Research Funding AstraZeneca Background: D consolidation after concurrent chemoradiotherapy (cCRT) improves survival in pts with uNSCLC. Rational immunotherapy combinations may further improve outcomes. As radiotherapy can induce expression of CD73, HLA-E (NKG2A ligand), and PD-L1 in tumor cells, all of which suppress antitumor immunity, there is a rationale for blockade of these immune checkpoints after cCRT. Interim results from COAST (NCT03822351), a global, open-label, Phase 2 study of D ± M (anti-NKG2A) or O (anti-CD73) as consolidation therapy in pts with Stage III uNSCLC, suggested improved progression free survival (PFS) with D+O and D+M vs D alone. We present updated efficacy and safety. Methods: Pts with histologically / cytologically documented Stage III uNSCLC and ECOG PS 0 / 1 with no progression after cCRT were randomized (1:1:1; stratified by histology) within 42 days post cCRT to receive D 1500 mg IV every 4 weeks (Q4W) for 12 months ± O 3000 mg IV Q2W for two cycles then Q4W or M 750 mg IV Q2W. Primary endpoint: objective response rate (ORR). Key secondary endpoints: safety, PFS, and overall survival (OS). Results: From Jan 2019 to Jul 2020, 186 of 189 randomized pts received treatment. Baseline characteristics were generally balanced across arms. As of Jul 18, 2023, median follow-up was 30.1 mo (range, 0.4–48.9). Of pts receiving D, D+O, and D+M, 69.7%, 44.1%, and 41.0% discontinued treatment (Tx), primarily due to progressive disease (42.4%, 18.7%, and 19.6%) or adverse events (AEs; 15.2%, 15.3%, and 14.8%). Median exposure was 7 cycles (range, 1–13) for D, and 13 (1–13) for D+O and D+M. ORR, PFS, and OS (39.6% maturity) are summarized in the Table. Tx-emergent AEs occurred in 98.5%, 96.6%, and 100% (Grade [G] 3/4: 34.8%, 33.9%, and 32.8%) of pts receiving D, D+O, or D+M, respectively; immune-mediated AEs (imAEs) occurred in 34.8%, 25.4%, and 34.4% (G 3/4: 3.0%, 0%, and 3.3%); and the AE of special interest pneumonitis occurred in 16.7%, 20.3%, and 18.0% (G 3/4: 0%, 0%, and 1.6%). Subgroup analyses and biomarker data will be presented. Conclusions: D+O and D+M increased ORR and prolonged PFS and OS vs D alone. Safety was similar across arms, with no new safety signals. Further investigation of D, D+O, and D+M in this population is ongoing in the Phase 3 PACIFIC-9 study (NCT05221840). Clinical trial information: NCT03822351. D (n=67) D+O (n=60) D+M (n=62) Confirmed ORR (95% CI), % 23.9 (14.3, 35.9) 35.0 (23.1, 48.4) 40.3 (28.1, 53.6) Complete / partial response, n (%) 2 (3.0) / 14 (20.9) 0 / 21 (35.0) 3 (4.8) / 22 (35.5) Median duration of response (95% CI), mo NR (14.1, NR) 29.9 (17.1, NR) 23.0 (10.2, NR) Median PFS (95% CI), mo 7.3 (4.0, 13.8) 21.1 (10.4, 30.9) 19.8 (13.6, 31.3) PFS HR (95% CI) - 0.59 (0.37, 0.93) 0.63 (0.40, 0.99) Median OS (95% CI), mo 40.9 (22.6, NR) NR (31.9, NR) NR (31.3, NR) OS HR (95% CI) - 0.69 (0.40, 1.20) 0.77 (0.44, 1.33) 2-year OS rate (95% CI), % 61.5 (47.4, 72.9) 76.8 (63.3, 85.8) 72.1 (58.6, 81.9) NR, not reached.

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