ASCO 2024: Adagrasib shows PFS benefit over docetaxel in previously treated KRASG12C-mutated NSCLC

In the phase 3 KRYSTAL-12 trial, adagrasib (ADA) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) and objective response rate (ORR) over docetaxel (DOCE) in patients with previously treated KRASG12C-mutated NSCLC. The safety profile of ADA was consistent with previous reports, with no new safety signals detected. These results further support ADA as a treatment option in this population.

• Pts with KRASG12C-mutated locally advanced or metastatic NSCLC, previously treated with platinum-based chemotherapy and anti-PD-(L)1 therapy, were randomized 2:1 to receive ADA (600 mg bid orally) or DOCE (75 mg/m^2 q3wks IV), with the ability to crossover to ADA upon disease progression. Primary endpoint was PFS. Secondary endpoints included ORR, duration of response (DOR), overall survival (OS), 1-year OS rate, and safety. In total, 301 pts were randomized to ADA and 152 to DOCE. Baseline characteristics were generally similar between treatment arms.
• With a median follow-up of 9.4 months, PFS was significantly improved with ADA over DOCE (median 5.49 vs. 3.84 months). ORR was also significantly higher with ADA compared with DOCE (31.9% vs. 9.2%); median DOR was 8.31 vs. 5.36 months, respectively.
• Treatment-related adverse events (TRAEs) were reported in 94.0% of patients treated with ADA and 86.4% with DOCE; grade ≥3 TRAEs occurred in 47.0% and 45.7% of pts, respectively. TRAEs led to discontinuation of ADA in 7.7% of patients and DOCE in 14.3%. Additional efficacy and safety analyses, including subgroup analyses, will be presented.

Source:

Mok, T., et al. KRYSTAL-12: Phase 3 study of adagrasib versus docetaxel in patients with previously treated advanced/metastatic non-small cell lung cancer (NSCLC) harboring a KRASG12C mutation. Abstract #LBA8509. Presented at: 2024 ASCO Annual Meeting; May 31 – June 4. Chicago, IL. https://meetings.asco.org/abstracts-presentations/232538