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).

Abstract

8046 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 . [Table: see text]

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