KEY TAKEAWAYS
- The study shared findings from a two-year follow-up of adagrasib monotherapy in patients with advanced/metastatic KRASG12C-mutated NSCLC.
- The study’s endpoints for both Cohorts were safety and efficacy (ORR, DOR, PFS, and OS).
- Adagrasib demonstrated durable clinical activity with manageable safety.
In the study, patients with advanced/metastatic non-small cell lung cancer (NSCLC) having KRASG12C mutations were administered adagrasib at 600 mg BID orally in the Phase 1/1b and Phase 2 Cohorts. The study endpoints for these Cohorts were safety and efficacy, such as ORR, DOR, PFS, and OS. Objective responses in tumors were evaluated according to RECIST v1.1 criteria, and assessments for ORR, DOR, and PFS were made by a blinded independent central review (BICR).
As of January 1, 2023, 132 pts with KRASG12C-mutated NSCLC were treated with adagrasib, comprising 16 pts from Phase 1/1b and 116 from Phase 2. The median duration of follow-up was 26.9 months (95% CI 25.9-29.7). The median age was 64 years, ranging from 25 to 89 years. Females comprised 56.8% of the population, and 19.7% had CNS metastases at the start. Most pts, 97.0%, had undergone platinum-based and checkpoint inhibitor therapies; the median number of prior therapies was 2.
The ORR was observed to be 43.0% among 128 evaluable pts; the median DOR was 12.4 months (95% CI 7.0-15.1). The median PFS was 6.9 months (95% CI 5.4-8.7), with a 1-year PFS rate of 35.0% (95% CI 25.9-44.2). The median OS was 14.1 months (95% CI 9.2-18.7); 1-year and 2-year OS rates were 52.8% and 31.3% respectively. Patients with co-mutations like KEAP1 (n=25), STK11 (n=44), and TP53 (n=42) had median OS of 5.7 months (95% CI 3.6-9.2), 9.2 months (95% CI 5.0-12.7), and 18.7 months (95% CI 11.3-27.0) respectively.
Those with CNS metastases at baseline showed a median OS of 14.7 months (95% CI 7.5-19.3). Grade ≥3 treatment-related adverse events (TRAEs) were seen in 61 pts (40.9% grade 3, 3.0% grade 4, 2.3% grade 5 [consisting of pneumonitis, cardiac failure, and pulmonary hemorrhage, with one case each]). TRAEs prompted dose reductions in 68 pts (51.5%), leading to treatment discontinuation in 12 pts (9.1%). In total, 32.6% of pts (43/132) had been on adagrasib for over a year.
In the extended follow-up of this combined analysis, adagrasib showed durable clinical activity, with a median OS of 14.1 months and nearly one-third of pts surviving at the two-year mark. Exploratory analyses indicated heterogeneity of clinical benefit depending on co-mutations, warranting additional investigation. The safety profile of adagrasib remained consistent with earlier findings and was manageable.
A Phase 3 trial that compares adagrasib as a monotherapy to docetaxel in pts with advanced KRASG12C-mutated NSCLC who have received prior treatment is underway.
Source: https://cattendee.abstractsonline.com/meeting/10925/presentation/1016
Clinical Trials: https://classic.clinicaltrials.gov/ct2/show/NCT03785249
https://classic.clinicaltrials.gov/ct2/show/NCT04685135
Gadgeel, S., Jänne, P.A., Spira, A.I., Ou, S-H.I., Heist, R.S., Pacheco, J.M., Johnson, M.L., Sabari, J.K., Leventakos, K., Mason, J.A., Velastegui, K., Yan, X., Chao, R., Riely, G.J. KRYSTAL-1: Two-Year Follow-Up of Adagrasib (MRTX849) Monotherapy in Patients with Advanced/Metastatic KRASG12C-Mutated NSCLC.
