Bristol Myers Squibb...announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for KRAZATI ® (adagrasib) in combination with cetuximab as a targeted treatment option for adult patients with KRASG12C -mutated locally advanced or metastatic colorectal cancer (CRC), as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

Mirati Therapeutics, Inc. (NASDAQ: MRTX), announced today that the FDA has granted BTD to adagrasib in combination with cetuximab in patients with KRASG12C-mutated, advanced CRC whose cancer has progressed following prior treatment with chemotherapy and an anti-VEGF therapy. This designation is supported by results from the Phase 1b cohort of the KRYSTAL-1 trial.

...- Histologically confirmed diagnosis of adenocarcinoma of the colon or rectum with KRASG12C mutation....

...- Histologically confirmed diagnosis of colorectal carcinoma with KRAS G12C mutation in tumor tissue....

In the combination-therapy group (28 evaluable patients), the response was 46% (95% CI, 28 to 66). The median response duration was 7.6 months (95% CI, 5.7 to not estimable), and the median progression-free survival was 6.9 months (95% CI, 5.4 to 8.1)....Adagrasib had antitumor activity in heavily pretreated patients with metastatic colorectal cancer with mutant KRAS G12C, both as oral monotherapy and in combination with cetuximab.

In 28 pts evaluable for efficacy, ORR was 46% (13/28) and DCR was 100% (28/28). Median DOR was 7.6 mo (95% CI 5.7–NE) and median PFS was 6.9 mo (95% CI 5.4–8.1)...Adagrasib is well tolerated as monotherapy and with cetuximab. Both showed clinical activity in heavily pretreated pts with KRASG12C-mutated CRC, with more sustained responses with the combination.

As of 9 July 2021, 32 pts with CRC (53% female; median age 60 years; 3 median prior lines of therapy) were treated with adagrasib + cetux (median follow-up 7 months)….Among the 28 pts evaluable for clinical activity, the response rate was 43% (12/28, including 2 unconfirmed PRs who remain on study) and DCR was 100%....Adagrasib is well tolerated as monotherapy and combined with cetux and demonstrates promising clinical activity in heavily pretreated pts with KRASG12C-mutant CRC.

The combination of MRTX849 plus cetuximab demonstrated the best anti-tumor activity in multiple models . The combination of MRTX849 and cetuximab demonstrated increased KRASG12C modification and MAPK pathway inhibition suggesting these therapies converge to more fully inhibit KRASG12C.