LBA4 Preliminary safety and efficacy of adagrasib with pembrolizumab in treatment-naïve patients with advanced non-small cell lung cancer (NSCLC) harboring a KRASG12C mutation

The combination of adagrasib (ada), a KRASG12C inhibitor, with an immune checkpoint inhibitor (CPI) has demonstrated enhanced preclinical anti-tumor activity. We report safety and efficacy ada + pembrolizumab (pembro) in patients (pts) enrolled the KRYSTAL-1 (NCT03785249) KRYSTAL-7 (NCT04613596) trials. In Ph 1b cohort 2 KRYSTAL-7, pts treatment-naïve, KRASG12C-mutated, advanced NSCLC received concurrent 400 mg BID pembro 200 Q3W. Pts were across all PD-L1 levels. Endpoints (objective response rate [ORR], duration [DOR], progression-free survival [PFS], overall [OS]). As 30 Aug 2022, 75 (median follow-up 3.5 mo) had evaluable. Median age was 66 yrs, 51% female, 35%/65% ECOG PS 0/1. Any grade treatment-related adverse events (TRAEs) occurred 83% pts; most common nausea (48%), diarrhea (43%) vomiting (24%). Grade 3–4 TRAEs 44% increased lipase (11%) ALT/AST (8%/9%), 3. There no 5 TRAEs. led to both discontinuation 3% pts. preliminary analysis tumor among 53 at least 1 on-study scan treatment mo), ORR 49% (26/53 [5 uPR]) disease control (DCR) 89%; 6 responses on second or later 56% ≥6 mo before data cut-off. DOR, PFS, OS not mature, still treatment. KRYSTAL-1, 7 19.3 clinically 57% (4/7), DCR 100%; ongoing >18 months responders. Safety consistent KRYSTAL-7. Additional analyses will be presented. largest dataset evaluating combined CPI as first-line for presented date, manageable toxicity encouraging efficacy.