41P Efficacy of first-line (1L) nivolumab (N) + ipilimumab (I) by tumor histologic subtype in patients (pts) with metastatic nonsquamous NSCLC (mNSQ-NSCLC)

Tumor histologic subtype (THS) has been reported to be a prognostic indicator for NSCLC; the solid subtype is associated with poor prognosis. 1L N + I has demonstrated durable, long-term clinical benefit vs chemotherapy (C) in pts with mNSCLC. Here we report exploratory analyses of overall survival (OS) with 1L N + I and association of biomarkers by mNSCLC THS using data from the CheckMate (CM) 227 and 568 trials. THS was assessed in pts with evaluable mNSQ-NSCLC tissue in CM 227 Part 1 (NCT02477826; ph 3; N + I vs C; n = 675) and in CM 568 Part 1 (NCT02659059; ph 2; N + I, single arm; n = 170) by 3 independent pathologists using a modified version of the WHO NSCLC classification system. Samples were classified as solid, acinar, or other THS per consensus on the predominant THS. Exploratory assessments included OS, tumor PD-L1, TMB, select somatic mutations (muts; TP53, KRAS, and STK11; FoundationOne CDx™), and gene expression analysis (GEA) by THS. Table 41PBiomarkers and OS by THSCM 227 Part 1aTHS-evaluable pts: CM 227 (N + I and C), 675 pts and CM 568 (N + I), 170 pts; solid, 59% and 45%; acinar, 26% and 28%; other, 10% and 7%; not specified, 5% and 19%, respectively.N + ICM 568 Part 1aTHS-evaluable pts: CM 227 (N + I and C), 675 pts and CM 568 (N + I), 170 pts; solid, 59% and 45%; acinar, 26% and 28%; other, 10% and 7%; not specified, 5% and 19%, respectively.N+ISolid (n = 192)Acinar (n = 91)Solid (n = 77)Acinar (n = 48)Median tumor PD-L1 expression, % (range)50 (0–100)1 (0–100)30 (0–100)0 (0–80)Median TMB, mut/Mb (range) OS8.8 (0–66.8)6.3 (0–44.1)10.1 (1.3–98.4)5.7 (1.3–17.6)Median, mo (95% CI)18.7 (13.5–28.4)13.3 (10.0–17.1)26.5 (14.6–47.3)12.9 (8.6–24.0)HR, solid vs acinar (95% CI)0.60 (0.45–0.80)–0.67 (0.44–1.02)–5-y rate, % (95% CI)31.0 (24.9–38.4)6.0 (2.6–14.0)31.1 (21.9–44.1)18.4 (9.9–34.3)a THS-evaluable pts: CM 227 (N + I and C), 675 pts and CM 568 (N + I), 170 pts; solid, 59% and 45%; acinar, 26% and 28%; other, 10% and 7%; not specified, 5% and 19%, respectively. Open table in a new tab Baseline characteristics were generally consistent across THS and treatment groups. Minimum follow-up was 61.3 and 61.2 mo in CM 227 and 568, respectively. In both trials, greater OS benefit was observed in N + I-treated pts with solid vs acinar THS (CM 227: HR 0.60, 95% CI 0.45–0.80; CM 568: HR 0.67, 95% CI 0.44–1.02; table). In contrast, among C-treated pts, OS was similar in pts with solid or acinar THS in CM 227 (HR 1.01, 95% CI 0.77–1.32). Further exploratory analysis identified a trend toward higher tumor PD-L1 expression and TMB in pts with solid vs acinar THS (table). A higher frequency of TP53 muts and lower frequencies of KRAS and STK11 muts were also observed in the solid THS. These results and findings from GEA by THS will be presented. Greater long-term OS benefit with N + I was seen in pts with the solid mNSCLC THS, a subgroup with poor prognosis, vs pts with the acinar THS. Exploratory PD-L1, TMB, and mut analysis may provide insight into the clinical benefit of 1L dual immunotherapy by THS.