8MO Adagrasib (MRTX849) in patients with advanced/metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC): Preliminary analysis of mutation allele frequency
Recommended Citation
Jänne PA, Spira A, Riely GJ, Gadgeel S, Heist R, Ou SHI, Johnson ML, Sabari J, Velastegui K, Christensen JG, Yang W, Anderes K, Chao R, and Paweletz C. 8MO Adagrasib (MRTX849) in patients with advanced/metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC): Preliminary analysis of mutation allele frequency. J Thorac Oncol 2023; 18(4):S41-S42.
Document Type
Conference Proceeding
Publication Date
4-2023
Publication Title
J Thorac Oncol
Abstract
Background: KRASG12C mutations occur in ~14% of NSCLC adenocarcinomas. Adagrasib (ada), a KRASG12C inhibitor, was selected for favorable properties, including long half-life (23 h), dose-dependent pharmacokinetics, and central nervous system penetration. In the KRYSTAL-1 registrational phase II Cohort A, ada showed clinical activity with manageable tolerability in patients (pts) with previously treated KRASG12C-mutated NSCLC.
Methods: Pts with previously treated KRASG12C-mutated NSCLC received ada 600 mg orally BID. Study objectives included objective response rate [ORR], progression-free survival [PFS], overall survival [OS], safety and exploratory correlative analyses. An exploratory analysis of clinical response for pts with detectable circulating tumor (ct) DNA at baseline, cycle 2 day 1, and cycle 4 day 1 (C4D1), who comprise the mutation allele frequency clearance (MAFC)-evaluable population, was also performed; KRASG12C ctDNA was assessed by digital droplet polymerase chain reaction.
Results: At data cutoff, 15 Oct 2021, Cohort A included 116 pts (median follow-up 12.9 months): median age 64 years, 56% female, median 2 prior systemic therapies. ORR by blinded independent central review (BICR) was 42.9%, disease control rate 79.5%, median PFS 6.5 months (95% CI 4.7–8.4) and, with longer follow-up (cutoff 15 Jan 2022), median OS 12.6 months (95% CI 9.2–19.2). Any grade treatment-related adverse events (TRAEs) occurred in 97% of pts (most commonly [>40%] diarrhea [63%], nausea [62%], vomiting [47%], and fatigue [41%]), and Grade 3–4 TRAEs in 43% (most commonly [≥5%] serum lipase increase [6%] and anemia [5%]). Two grade 5 TRAEs occurred; 8 (7%) TRAEs led to discontinuation. In MAFC-evaluable pts (n = 35), ORR by BICR was 60% (21/35) and all responses correlated with MAFC >90% by C4D1.
Conclusions: Ada showed promising efficacy and manageable tolerability in previously treated pts with KRASG12C-mutated NSCLC. Additional analyses are needed to further evaluate whether clinical response with ada correlates with MAFC in ctDNA. A phase III trial evaluating ada monotherapy vs docetaxel in previously treated pts with KRASG12C-mutated NSCLC is ongoing (NCT04685135). Clinical trial identification NCT03785249.
Volume
18
Issue
4
First Page
S41
Last Page
S42