Mirati details early results for KRAS inhibitor MRTX849

Mirati Therapeutics presented the first results from a Phase I/II trial of MRTX849, with data showing that the experimental KRAS G12C inhibitor was associated with a partial response (PR) rate of 40% in 10 patients with non-small-cell lung cancer (NSCLC) or colorectal cancer (CRC). The findings were reported at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.

The ongoing study has enrolled 17 patients with molecularly-identified, KRAS G12C-positive advanced solid tumours, including 10 subjects with NSCLC, four people with CRC and three individuals with other tumour types. Mirati noted that five dose cohorts have so far been evaluated, while the maximum tolerated dose has not yet been established and the trial continues to enrol patients.

According to the company, as of the data cut-off of October 11, 12 patients were evaluable for response with at least one radiographic scan. Results showed that at the highest dose, three of five evaluable patients with NSCLC and one of two evaluable subjects with CRC achieved a PR, while the remaining patients experienced stable disease. Further, across all dose levels, three of six patients with NSCLC and one of four individuals with CRC achieved a PR. Mirati added that two responding patients, one with NSCLC and one with CRC, achieved confirmed PRs, both with continuing tumour shrinkage following their first scan.

"The signs are there, but the numbers are small," remarked lead investigator Pasi Janne, adding "it is too early to say anything about the durability of response." Janne indicated that side effects in the study have mostly been mild, including diarrhoea and nausea. However, one patient experienced a dose-limiting toxicity of grade 3/4 isolated amylase/lipase increase.

Last month, Amgen reported the first data from a Phase I study of its experimental oral KRAS inhibitor AMG 510 in CRC patients with previously treated KRAS G12C-mutated solid tumours. Results showed that in 12 patients who received the target dose of 960 mg once daily, one experienced a PR and 10 had stable disease for a disease control rate of 92%. The company previously disclosed that in 13 evaluable patients with NSCLC, 54% experienced a PR at the target dose of 960 mg, while 46% had stable disease.

For related analysis, see ViewPoints: Some bloom comes off Amgen's KRAS rose, and Spotlight On: Key questions from ESMO 2019.

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