KEY TAKEAWAYS
- The KRYSTAL-7 phase II/III trial aimed to assess the expanded efficacy and safety profile of ada+pembro in treatment-naïve KRASG12C+ NSCLC.
- The study’s objective was to determine efficacy, ORR, DOR, PFS, OS, and safety.
- The result demonstrated promising efficacy and safety for ada + pembro in KRASG12C+ NSCLC with PD-L1 ≥50%, paving the way for Phase 3 vs. pembro alone.
Adagrasib(ada), a KRASG12C inhibitor with potential CNS penetration and lower off-target effects, shows promise in early combination with pembrolizumab(pembro) for KRASG12C+ nonsmall cell lung cancer(NSCLC).
Researchers aimed to assess the expanded efficacy and safety profile of ada+pembro in a larger cohort of KRASG12C-mutant NSCLC patients, building upon the initial findings of the KRYSTAL-7 trial.
Treatment-naïve patients with KRASG12C-mutated advanced NSCLC were administered concurrent ada 400 mg orally twice daily (BID) along with pembro 200 mg intravenously every 3 weeks (Q3W).
The study aimed to assess efficacy through investigator-assessed objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival(OS). Safety was also an important aspect of the study evaluation.
About 148 patients received ada+pembro with a median follow-up of 8.7 months. The median age was 67, 48% females and 39%/61% having ECOG PS 0/1. In patients with PD-L1 ≥50% (median follow-up 10.1 months), ORR was 63% (32/51 patients), and the disease control rate was 84%.
The median DOR was not reached (NR; 95% CI 12.6–NE), and the median PFS was also not reached (NR; 95% CI 8.2–NE) for this subgroup. Overall, treatment-related adverse events (TRAEs) of any grade occurred in 94% (139/148) of patients, with 55% being grade 3, 9% grade 4, and 1% grade 5.
TRAEs led to the discontinuation of ada and pembro in 4% of patients (6% discontinued ada alone, 11% discontinued pembro alone). No patient discontinued both drugs due to ALT/AST increase or hepatic TRAEs, while 1 patient discontinued ada and 3 discontinued pembro due to liver transaminase elevation. Further efficacy and safety analyses will be presented.
The result demonstrated promising efficacy and safety for adagrasib + pembro in KRASG12C+ NSCLC with PD-L1 ≥50%, paving the way for Phase 3 vs. pembro alone.
Clinical Trial: https://clinicaltrials.gov/study/NCT04613596
M.C. Garassino, W.S.M.E. Theelen, R. Jotte, J. Laskin, F. de Marinis, C. Aguado, F.B. Badin, I. Chmielewska, M.J. Hochmair, S. Lu, E. Nadal, G. Ostoros, E. Felip, A.I. Spira, C.M. Lane, J. He, R. Chao, P.A. Jänne. “KRYSTAL-7: Efficacy and safety of adagrasib with pembrolizumab in patients with treatment-naïve, advanced non-small cell lung cancer (NSCLC) harboring a KRASG12C mutation.” Annals of Oncology (2023) 34 (suppl_2): S1254-S1335. DOI: 10.1016/annonc/annonc1358. LBA65.
