LBA42 COAST: An open-label, randomised, phase II platform study of durvalumab alone or in combination with novel agents in patients with locally advanced, unresectable, stage III NSCLC

PACIFIC established consolidation durvalumab (D) as SoC for unresectable Stage III NSCLC with no progression after cCRT. Combination therapy may improve outcomes. CD73 is involved in RT resistance. RT induces NKG2A ligand and shows additive antitumour effects with PD-1 blockade preclinically. COAST (NCT03822351) is a global phase 2 study of D alone or combined with the anti-CD73 mAb oleclumab (O) or anti-NKG2A mAb monalizumab (M) as consolidation therapy. Pts with histologically/cytologically documented unresectable Stage III NSCLC, ECOG PS 0/1 and no progression after cCRT were randomised 1:1:1 ≤42 days post cCRT to receive D 1500 mg IV Q4W alone or combined with O 3000 mg IV Q2W (first 2 cycles, then Q4W) or M 750 mg IV Q2W for up to 12 months, stratified by histology. The primary endpoint was investigator-assessed post cCRT ORR per RECIST v1.1. Key secondary endpoints included PFS and safety. Between Jan 2019 and Jul 2020, 189 pts were randomised, of whom 186 received D (n=66), D+O (n=59) or D+M (n=61). As of 17 May 2021, median follow-up was 11.5 months (range, 0.4–23.4; all pts). D+O and D+M numerically increased ORR (odds ratio [95% CI] 1.83 [0.80, 4.20] and 1.77 [0.77, 4.11] respectively) and significantly improved PFS versus D alone. Grade ≥3 treatment-emergent AE (TEAE, all-cause) incidence was 39.4%, 40.7% and 27.9% with D, D+O and D+M respectively. Overall, the most common grade 3/4 TEAEs were pneumonia (5.9%) and decreased lymphocyte count (3.2%); both were more common with D and D+O than with D+M. Combined rates of pneumonitis and radiation pneumonitis of any grade were 21.2% with D, 28.8% with D+O and 21.3% with D+M, with grade ≥3 events in 3.0%, 3.4% and 1.6%. Biomarker data will be presented. Addition of both novel agents improved ORR, PFS and 10-month PFS rate over D alone. Safety was similar across arms with no new safety signals identified.Table: LBA42ITTDD+OD+MN676062ORR (95% CI), %a,b25.4 (15.5, 37.5)38.3 (26.1, 51.8)37.1 (25.2, 50.3)Objective responses, na172323CR, n (%)2 (3.0)1 (1.7)3 (4.8)PR, n (%)15 (22.4)22 (36.7)20 (32.3)Median PFS (95% CI), moc6.3 (3.7, 11.2)NR (10.4, NE)15.1 (13.6, NE)PFS HR (95% CI)d,e-0.44 (0.26, 0.75)0.65 (0.49, 0.85)10-month PFS rate (95% CI), %c39.2 (26.1, 52.0)64.8 (50.4, 76.0)72.7 (58.8, 82.6)aConfirmed and unconfirmed b95% CI by Clopper-Pearson exact method c10-month minimum follow-up for all pts; Kaplan-Meier estimates for PFS, PFS rate and 95% CIsdPFS HR and 95% CI estimated by Cox regression model, stratified by histology eCompared to 67 D+O pts and 64 D+M pts enrolled concurrently with D pts Open table in a new tab