Amgen Announces Promising Clinical Results of KRAS Inhibitor AMG 510 in Colorectal and Appendiceal Cancers

Recently, Amgen announced the latest research and development progress of its KRAS G12C inhibitor AMG 510 during a conference call for its second-quarter 2019 financial report. The latest trial data indicate that AMG 510 not only demonstrates efficacy in patients with non-small cell lung cancer (NSCLC), but also provides partial response in patients with colorectal cancer (CRC) and appendiceal cancer. Based on these positive results, the company plans to accelerate the development of AMG 510 and initiate potential registration-enabling clinical trials supporting regulatory applications this year.

The RAS gene family is among the most frequently mutated oncogenes in human cancers and has been a major focus of drug development for over three decades. Mutations in the KRAS gene are particularly common in solid tumors, with the KRAS G12C mutation occurring in 13% of patients with non-small cell lung cancer (NSCLC), 2% of patients with colorectal cancer (CRC), and 1–2% of patients with other solid tumors. However, due to the lack of a “pocket” for binding traditional small-molecule drugs, the KRAS protein has long been considered an “undruggable” target.

Amgen and other biotechnology companies have identified the binding site for small-molecule drugs on the KRAS G12C mutant through structural studies, making it possible to target this mutant.

▲Introduction to AMG 510 (Image source: Amgen official website)

At the ASCO Annual Meeting held in June this year, Amgen presented for the first time the Phase 1 clinical trial results of AMG 510, a KRAS G12C inhibitor. All patients enrolled in the trial harbored the KRAS G12C mutation and had previously received standard-of-care therapy. Among the 10 evaluable patients with non-small cell lung cancer (NSCLC), the objective response rate was 50%, and the disease control rate was 90%. However, data at that time indicated that AMG 510 only achieved stable disease in patients with colorectal cancer, without significantly reducing tumor size.

Latest data indicate that one patient with colorectal cancer and one with appendiceal cancer achieved clinical response per RECIST 1.1 criteria while receiving AMG 510. Both patients were treated with AMG 510 at a dose of 960 mg, the highest dose level in the dose-escalation trial. Dr. David Reese, Executive Vice President of Research and Development at Amgen, stated that AMG 510 demonstrated favorable safety and tolerability in the trial. Future clinical trials will use the 960 mg dose and may explore doses exceeding 960 mg.

▲Latest R&D Information on AMG510 (Image source: Amgen official website)

During the second-quarter conference call, Amgen executives stated that preclinical studies indicated AMG 510 may have a synergistic effect with immune checkpoint inhibitors in cancer treatment, and therefore clinical trials combining AMG 510 with PD-1 inhibitors will be conducted. Meanwhile, the company plans to initiate a registrational Phase 2 clinical trial. At the IASLC 2019 World Conference on Lung Cancer held in early September, the company will present the latest clinical results of AMG 510 in the treatment of lung cancer.

References:

[1] UPDATED: Amgen's KRAS drug shows promise in 2 additional cancers: colorectal and appendiceal. Retrieved July 31, 2019, from https://www.fiercebiotech.com/biotech/amgen-s-kras-drug-hits-mark-2-additional-cancers-colorectal-and-appendiceal

[2] Amgen Q2’ 19 Earnings Call. Retrieved July 31, 2019, from http://investors.amgen.com/static-files/e1393dc2-f372-4dcc-992a-afc36a03b8fa

[3] Amgen Announces First Clinical Data Evaluating Novel Investigational KRASG12C Inhibitor AMG 510 At ASCO 2019. Retrieved July 31, 2019, from https://www.amgen.com/media/news-releases/2019/06/amgen-announces-first-clinical-data-evaluating-novel-investigational-krasg12c-inhibitor-amg-510-at-asco-2019/

[4] AMGEN AT ASCO 2019: ADVANCING A PORTFOLIO OF NOVEL, HIGH-POTENTIAL CANCER THERAPIES. Retrieved July 31, 2019, from http://investors.amgen.com/static-files/f283e23c-5194-4d2a-be5f-07fb24d1ecec

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