KRYSTAL-1

Previously, the phase 1/2 KRYSTAL-1 study demonstrated promising clinical activity with the combination of adagrasib (irreversible inhibitor of KRAS^G12C) and cetuximab (anti-EGFR) in patients with previously treated KRAS^G12C-mutated metastatic colorectal cancer (mCRC) (overall response rate [ORR] per investigator: 43%). During ASCO GI 2025, Dr Rona Yaeger, medical oncologist at the Memorial Sloan Kettering Cancer Center in New York, shared longer follow-up data of this trial. After a median follow-up of 20.4 months, the investigator-assessed ORR was confirmed at 43% (all partial responses), with a median response duration of 5.9 months. The median progression-free survival (PFS) was reported at 6.9 months, with a 1-year PFS rate of 19%. The median overall survival reached 16.0 months, with 66% of patients being alive after 1 year. Overall, 28% of patients suffered a grade ≥3 adverse event.

As such, these updated results are consistent with those from the primary analysis. The efficacy of second-line adagrasib + cetuximab in KRAS^G12C-mutated mCRC is currently being compared to that of chemotherapy in the phase 3 KRYSTAL-10 study.