Sotorasib 960 mg vs. 240 mg in pretreated KRAS G12C high-grade non-small cell lung cancer

Sotorasib (Sotorasib) 960mg daily is approved for pretreatment of KRASG12C advanced non-small cell lung cancer. Due to its non-linear pharmacokinetics (PK) and clinical responses observed at lower doses, we evaluated sotoraxib960 in an open-label Phase 2 post-marketing study (NCT03600883) mg and 240 mg.

AdultsKRASG12CAdults with advanced non-small cell lung cancer were randomized in a 1:1 ratio to once-daily sotoraxib 960 mg or 240 mg. Eligibility criteria included prior PD-(L)1 inhibitors and / or platinum-based chemotherapy and ECOG PS ≤ 2. The primary endpoints were BICRand safety RECIST 1.1objective response rate(ORR). Secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and PK. Efficacy results were considered descriptive and dose was assessed from the total data.

Baseline data were similar in patients randomized to receive either sotorcoxib960 mg (n=104)or240 mg (n=105). The ORR/DCR of the 960mg group was 32.7%/86.5%, while the 240mg group was 24.8%/81.9%. The median disease-free survival was 5.4 months in the 960mg group compared with 5.6 months(HR: 0.95 [95% CI: 0.67, 1.35]). The median follow-up time was 17.5 months, and the median OS was 13.0 months in the 960 mg group and 240 months in the 960 mg group. mg group was 11.7 months (HR 0.75 [95% CI: 0.53, 1.07]). The geometric meanCmaximum240mg is 22% lower than 960mg. Treatment-relatedAE(trae) are reported in the table. The most common trae(960mg vs 240mg)are diarrhea(35.6% vs 21.2%) and nausea(15.4% vs 13.5%), ALTelevated (11.5% vs 13.5%) and ASTelevated (10.6% vs 11.5%).

Sotoraxib960 compared to 240 mg mghad higher ORR/DCR and improved OS, with a higher ≥3 gradeTRAEs ratio. AEs at both doses were generally manageable with label-directed dose adjustments. CodeBreaK 300Supported by research KRASG12C mCRC , sotoraxib (960 mg and 240 mg) and panitumumabBoth doses showed statistically superior PFS to standard treatment, with the 960 mg dose showing clinical advantage. Overall, taking 960mg of sotoracil per day provided a more favorable benefit-risk profile.