Sotorasib in advanced KRAS p.G12C-mutated non-small cell lung cancer (NSCLC): Safety and efficacy data from the global expanded access program (EAP)

The sotorasib EAP provided compassionate use of sotorasib, a first-in-class KRAS G12C inhibitor, prior to local regulatory approvals. Here we present data from 2 global protocols under the EAP (Amgen study 20190436 [study-436] and 20190442 [study-442]) evaluating the safety and efficacy of sotorasib in patients (pts) with advanced KRAS p.G12C–mutated NSCLC beyond the traditional registrational trial setting. Pts, including those with ECOG PS 2, treated or untreated brain metastases, and additional co-morbidities, were enrolled in 6 countries (USA, ITA, BRA, ISR, ESP, TWN) across 52 centers. The study was primarily designed to assess the safety of sotorasib 960 mg QD. Real-world progression-free survival (rwPFS) was estimated for study-436 (allowed for long-term follow-up) based on time from start of treatment to end of protocol due to disease progression or death, any death before new anti-cancer therapy, or end of commercial sotorasib, whichever occurred earlier. Under 2 EAP protocols, 137 pts received sotorasib. At baseline, pts had received a median of 2 (up to 7) prior lines of anticancer therapy, 29 (21%) pts had ECOG PS 2, and 36 (26%) had brain metastases (75% treated, 25% untreated). Grade ≥ 3 treatment-related adverse events (TRAEs) occurred in 32 (23%) pts; elevated AST and ALT (both 7 [5%] pts) were the most frequent. No suspected Hy’s law cases occurred. TRAEs leading to discontinuation and dose interruption/reduction of sotorasib occurred in 9 (7%) and 34 (25%) pts, respectively. TRAEs were similar, regardless of ECOG status or brain metastases at baseline. In study-436, median rwPFS was 6.4 months and subgroups of clinical interest are summarized (Table).Table: 989PMedian rwPFS, months (95% CI)aStudy-436 patients (n = 92)6.4 (4.6–7.6)bSubgroups (at baseline)ECOG Performance Status0 (n = 12)6.4 (2.7–NE)1 (n = 56)6.2 (3.6–8.6)2 (n = 24)6.5 (3.4–7.7)Brain metastasisYes (n = 24)4.7 (2.7–7.6)No (n = 68)6.7 (4.6–9.1)CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; NE, not estimable; rwPFS, real-world progression-free survivalaIn study-436, 30/92 (33%) patients switched to commercial supply. Patients who discontinued commercial supply were deemed to have progressed.bMedian follow-up was 7.4 months; data cut-off date: April 1, 2022. Open table in a new tab CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; NE, not estimable; rwPFS, real-world progression-free survival aIn study-436, 30/92 (33%) patients switched to commercial supply. Patients who discontinued commercial supply were deemed to have progressed. bMedian follow-up was 7.4 months; data cut-off date: April 1, 2022. In this first analysis of the sotorasib EAP, which included pts with poor ECOG status and untreated brain metastases, the safety and rwPFS of sotorasib were consistent with the profile observed in clinical trials. Table