1442P Association of TMB using the Foundation Medicine Companion Diagnostic (F1CDx) with efficacy of first-line pembrolizumab (pembro) or pembro plus chemotherapy (pembro + chemo) versus chemo in patients with gastric cancer (gc) from KEYNOTE-062

Abstract

In the phase III KEYNOTE-062 study (NCT02494583) in advanced GC or gastroesophageal junction adenocarcinoma (N = 763), first-line pembro was noninferior to chemo for OS in patients with PD-L1 CPS ≥1 but showed clinically meaningful improvement in patients with CPS ≥10; pembro + chemo did not show superior survival in patients with CPS ≥1 or in patients with CPS ≥10. We explored the association of TMB status and clinical outcomes in KEYNOTE-062. In patients with available TMB data, the association of TMB (square root scale), assessed via F1CDx, with clinical outcomes was evaluated. Within each treatment group, confirmed ORR and PFS by blinded central radiology review per RECIST v1.1 and OS were evaluated using logistic regression (ORR) and Cox proportional hazards regression (PFS; OS) to calculate 1-sided (pembro; pembro + chemo) and 2-sided (chemo) P values. The clinical utility of TMB was assessed using the prespecified cutoff of 10 mut/Mb. Clinical data cutoff: March 26, 2019. 306/763 patients (40%) had evaluable TMB data (pembro, 107; pembro + chemo, 100; chemo, 99). The overall prevalence of TMB ≥10 mut/Mb was 16%. The sample size of patients with high or low TMB was balanced across the 3 groups. TMB was significantly associated with ORR, PFS, and OS with pembro and pembro + chemo (P < 0.05) but not with chemo (P > 0.05). Patient outcomes by TMB cutoff are reported in the TableTable: 1442PTMB≥10TMB≥10TMB<10TMB<10P (n=18) vs C (n=17)P+C (n=15) vs C (n=17)P (n=89) vs C (n=82)P+C (n=85) vs C (n=82)ORR, % (95% CI)56 (31-79) vs 41 (18-67)73 (45-92) vs 41 (18-67)7 (3-14) vs 48 (36-59)46 (35-57) vs 48 (36-59)PFS, HR (95% CI)0.52 (0.24-1.13)0.62 (0.39-0.97)1.73 (1.26-2.38)0.97 (0.82-1.14)OS, HR (95% CI)0.34 (0.14-0.82)0.54 (0.33-0.89)1.41 (1.02-1.95)1.01 (0.86-1.20)HRs are adjusted for ECOG PS. Open table in a new tab . HRs are adjusted for ECOG PS. This prespecified exploratory analysis from the randomized KEYNOTE-062 trial provides evidence of an association between TMB and clinical response with first-line pembro monotherapy and pembro + chemo but not with chemo in patients with GC. Data further suggest a survival benefit in pembro-treated patients with TMB ≥10 mut/Mb, which include a majority of patients with tumors with high microsatellite instability.