...the U.S. Food and Drug Administration (FDA) has accepted for priority review the supplemental new drug application (sNDA) for KRAZATI® (adagrasib) in combination with cetuximab for the treatment of patients with previously treated KRASG12C-mutated locally advanced or metastatic colorectal cancer (CRC).

Mirati Therapeutics...announced the United Kingdom's Medicines and Healthcare Products Regulatory Agency (MHRA) granted conditional marketing authorization approval for KRAZATI® (adagrasib) as a monotherapy indicated for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with KRASG12C mutation and have progressive disease after prior therapy with, or intolerance to, platinum-based chemotherapy and/or anti-PD-1/PD-L1 immunotherapy.

...- Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 1b must be either Non-Small Cell Lung Cancer or Colorectal Cancer)...

...- Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation...

...- KRASG12C-mutated solid malignancy determined by a sponsor-approved assay using either tumor tissue or ctDNA....

...MRTX0902 and adagrasib combination therapy: KRAS G12C mutation....

...- Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer)...

In the monotherapy group (43 evaluable patients), a response was reported in 19% of the patients (95% confidence interval [CI], 8 to 33). The median response duration was 4.3 months (95% CI, 2.3 to 8.3), and the median progression-free survival was 5.6 months (95% CI, 4.1 to 8.3)....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.

Patients with advanced KRASG12C-mutant solid tumors were treated with adagrasib...Of these 20 patients, the primary diagnosis was KRASG12C-mutant non–small-cell lung cancer (NSCLC; n = 16), KRASG12C-mutant CRC (n = 2), and KRASG12C-mutant mucinous appendiceal carcinoma (n = 2), respectively. One of two patients with KRASG12C-mutant colorectal cancer treated at 600 mg twice a day achieved a partial response (duration of response, 4.2 months).

Among the 45 pts evaluable for clinical activity, the response rate was 22% (10/45, including 1 unconfirmed PR who remains on study) and DCR was 87% (39/45). Median DOR was 4.2 months; median PFS was 5.6 months….Adagrasib is well tolerated as monotherapy and combined with cetux and demonstrates promising clinical activity in heavily pretreated pts with KRASG12C-mutant CRC.

17% (3/18) of evaluable CRC patients had a confirmed objective response...Disease control was observed in 94% (17/18) of patients...Six patients in the other solid tumor cohort were evaluable for clinical activity. Confirmed partial responses (PRs) were observed in a patient with endometrial cancer and a patient with pancreatic cancer (n=1/1 each); unconfirmed PRs were observed in patients with ovarian cancer and CCA (n=1/1 each).

...phase I trial 17 patients with solid tumors bearing KRAS G12C mutations….The initial MRTX849 dose of 150 mg once daily was escalated to doses up to 1,200 mg daily…Of the four evaluable patients with colorectal cancer, one had a confirmed partial response....treatment with MRTX849 was well tolerated...