A Review published in the Journal of Hematology & Oncology examines the current strategies for targeting specific KRAS mutations as well as strategies to target other related pathways.
]. The ORR was only 9.7% , and though 82.3% achieved disease control, the overall median PFS was only 4.0 months. In 38 patients with pancreatic cancer, sotorasib led to an ORR of 21.1% and DCR of 84.2% [Adagrasib monotherapy was studied in the phase I/II KRYSTAL-1 trial. The phase I portion utilized an accelerated titration design to explore doses of 150 mg daily, 300 mg daily, 600 mg daily, 1200 mg daily, and 600 mg twice daily [].
The phase II portion of KRYSTAL-2 included 116 patients with KRAS G12C NSCLC treated with adagrasib 600 mg bid []. All patients had prior platinum-doublet chemotherapy and 98.3% had received both chemotherapy and checkpoint inhibitor therapy. With a median follow-up of 12.9 months, the ORR was 42.9%. The time to response was 1.4 months and the median duration of response was 8.5 months. Median PFS was 6.5 months; with extended follow-up to 15.6 months, the median survival was 12.6 months .
Adagrasib has shown efficacy in patients with KRAS G12C NSCLC with treated and untreated brain metastases. Among 33 patients with previously treated, stable central nervous system metastases, the intracranial confirmed objective response rate was 33.3% [
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