Amgen's KRAS G12C Inhibitor AMG 510 Shows 80% Disease Control Rate in Colorectal Cancer and Activity Across Multiple Solid Tumors

By Baihuawen

Source:PharmaCube Info

On May 29, the ASCO 2020 conference announced multiple clinical data sets on Amgen’s AMG 510 for the treatment of patients with colorectal cancer and other solid tumors harboring KRAS G12C mutations.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide and the third most common cancer globally, with its incidence projected to increase by more than 20% over the next decade. Currently, among patients with metastatic CRC receiving standard treatment, the median progression-free survival (PFS) is approximately 2 months, and the response rate is less than 2%.

The Phase I dose-escalation study presented here evaluated 42 patients with advanced KRAS G12C-mutated colorectal cancer (CRC), of whom 69% had received more than three prior lines of therapy. As of January 2020, treatment duration exceeded 3 months in 22 (52.4%) patients and 6 months in 8 (19.0%) patients.

The results showed that the objective response rate (ORR) in the 960 mg/d dose group was 12% (3/25), and the disease control rate (DCR) was 80% (20/25). The median progression-free survival (PFS) was 4.2 months. At a median follow-up of nearly 8 months, the median overall survival (OS) had not been reached. Among the 23 patients with post-baseline data available, 11 patients experienced tumor shrinkage.

Across all dose groups, disease control was achieved in the majority of patients, with an objective response rate (ORR) of 7.1% and a disease control rate (DCR) of 76.2%. The median duration of stable disease was 4.2 months. The median progression-free survival (PFS) was 4.0 months, and the median overall survival (OS) was 10.1 months. Among the 39 patients with post-baseline data available, 18 experienced tumor shrinkage.

In terms of safety, the most common reason for discontinuation was disease progression. Treatment-related adverse events (TRAEs) were mostly Grade 1 and 2, with only two cases of Grade 3 TRAEs (diarrhea and anemia); no Grade 4 or higher TRAEs occurred.

In the treatment of 25 patients with other advanced KRAS G12C-mutant solid tumors (excluding CRC or NSCLC), AMG510 also demonstrated consistent antitumor activity and a favorable safety profile, including in pancreatic cancer, appendiceal cancer, and endometrial cancer. These patients had received a median of 3 prior lines of therapy, and the median follow-up time was 4.3 months.

Data showed that three patients with appendiceal cancer, melanoma, and endometrial cancer, respectively, achieved partial response. Among eight pancreatic cancer patients evaluable for efficacy, six had stable disease, and three patients exhibited a 30% reduction in tumor burden compared to baseline. Among 19 patients evaluable for efficacy, 13 experienced tumor shrinkage.