Abstract
The phase I trial of sotorasib, a KRASG12C inhibitor, demonstrated a favorable safety profile and preliminary antitumor activity in pts with advanced solid tumors harboring KRAS p.G12C. Here, we present durability of clinical benefit and biomarker data in pts with NSCLC. Key eligibility criteria include KRAS p.G12C mutation and prior systemic anticancer treatment (tx). Primary endpoint is safety; key secondary endpoints include objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and progression-free survival (PFS). KRAS p.G12C mutant allele frequency (MAF) and PD-L1 level were examined. As of July 17, 2019, 40 pts with NSCLC (22 female [55.0%], median age: 68.0 years [range: 49-77]) were enrolled. Data cutoff date was March 25, 2020. 31 (77.5%) and 19 pts (47.5%) received ≥ 2 and 3 prior lines of therapy, respectively. Median follow-up was 10.2 (range: 8.3–19.0) months (mos). 3 pts (7.5%) had adverse events leading to discontinuation. There were no dose-limiting toxicities or fatal tx-related adverse events. Median PFS for all pts was 6.9 (range: 1.2–13.9) mos. ORR was 30% (95% Cl, 16.56–46.53). DOR ranged from 1.6 (+) to 12.7 mos, with 7 of 12 responders still in response at data cutoff. DCR was 92.5% (95% Cl, 79.61–98.43). 18 pts (45.0%) had progressive disease. At data cutoff, 10 pts (25.0%) were on study without disease progression, and 9 pts (22.5%) died. 18 pts (45.0%) (5 partial response (PR), 12 stable disease (SD), 1 progressive disease (PD)) had KRAS p.G12C MAF data available. There was no significant association between KRAS p.G12C MAF and response (Wilcoxon P = 0.80 for PR vs SD). 11 pts (27.5%) had PD-L1 data available. The median PD-L1 tumor proportion score [TPS] was 3% (range: 1–5) in 2 pts with PR, 0% (range: 0–0) in 8 pts with SD, and 75% (range: 75–75) in the pt with PD (Wilcoxon P = 0.044 for PR vs. SD). In pts with heavily pretreated NSCLC, durable responses to sotorasib were seen, with the majority of pts achieving disease control leading to a median PFS of 6.9 months. The current limited dataset suggests that neither KRAS p.G12C MAF nor PD-L1 expression level predicts response to sotorasib.
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