Adagrasib in Advanced Solid Tumors Harboring a KRASG12C Mutation

PURPOSE Adagrasib, a KRAS(G12C) inhibitor, has demonstrated clinical activity in patients with KRAS(G12C)-mutated non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). KRAS(G12C) mutations occur rarely in other solid tumor types. We report evaluation of the clinical activity and safety of adagrasib in patients with other solid tumors harboring a KRAS(G12C) mutation.METHODSIn this phase II cohort of the KRYSTAL-1 study (ClinicalTrials.gov identifier: NCT03785249; phase Ib cohort), we evaluated adagrasib (600 mg orally twice daily) in patients with KRAS(G12C)-mutated advanced solid tumors (excluding NSCLC and CRC). The primary end point was objective response rate. Secondary end points included duration of response, progression-free survival (PFS), overall survival, and safety.RESULTS As of October 1, 2022, 64 patients with KRAS(G12C)-mutated solid tumors were enrolled and 63 patients treated (median follow-up, 16.8 months). The median number of prior lines of systemic therapy was 2. Among 57 patients with measurable disease at baseline, objective responses were observed in 20 (35.1%) patients (all partial responses), including 7/21 (33.3%) responses in pancreatic and 5/12 (41.7%) in biliary tract cancers. The median duration of response was 5.3 months (95% CI, 2.8 to 7.3) and median PFS was 7.4 months (95% CI, 5.3 to 8.6). Treatment-related adverse events (TRAEs) of any grade were observed in 96.8% of patients and grade 3-4 in 27.0%; there were no grade 5 TRAEs. TRAEs did not lead to treatment discontinuation in any patients.CONCLUSION Adagrasib demonstrates encouraging clinical activity and is well tolerated in this rare cohort of pretreated patients with KRAS(G12C)-mutated solid tumors.

Automated summary

The study evaluated the clinical activity and safety of adagrasib in patients with other solid tumors harboring a KRAS(G12C) mutation. The results demonstrated encouraging clinical activity and good tolerability of adagrasib in this rare cohort of pretreated patients with KRAS(G12C)-mutated solid tumors.