Amgen Announces First Clinical Data Evaluating Investigational KRAS(G12C) inhibitor AMG 510 at ASCO 2019

AMG 510 is the First KRAS^G12C Inhibitor to Reach Clinical Stage After Three Decades of RAS Research

First-In-Human Results Show Preliminary Data and Anti-Tumour Activity
in KRAS Mutant Solid Tumours

MISSISSAUGA, ON, June 5, 2019 /CNW/ - Amgen today announced the first clinical results from a Phase 1 study evaluating investigational AMG 510, the first KRAS^G12C inhibitor to reach the clinical stage. In the trial, there were no dose-limiting toxicities at tested dose levels. AMG 510 showed anti-tumour activity when administered as a monotherapy in patients with locally-advanced or metastatic KRAS^G12C mutant solid tumours. These data were presented during an oral session at the 55^th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

"KRAS has been a target of active exploration in cancer research since it was identified as one of the first oncogenes more than 30 years ago, but it remained undruggable due to a lack of traditional small molecule binding pockets on the protein. AMG 510 seeks to crack the KRAS code by exploiting a previously hidden groove on the protein surface," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "By irreversibly binding to cysteine 12 on the mutated KRAS protein, AMG 510 is designed to lock it into an inactive state. With high selectivity for KRAS^G12C, we believe investigational AMG 510 has potential as both a monotherapy and in combination with other targeted and immune therapies."

The Phase 1, first-in-human, open-label multicenter study enrolled 35 patients with various tumour types (14 non-small cell lung cancer [NSCLC], 19 colorectal cancer [CRC] and two other). Eligible patients were heavily pretreated with at least two or more prior lines of treatment, consistent with their tumour type and stage of disease. The primary endpoint is safety, and key secondary endpoints include pharmacokinetics, objective response rate (assessed every six weeks), duration of response and progression-free survival. Patients were enrolled in four dose cohorts - 180 mg, 360 mg, 720 mg and 960 mg, taken orally once a day.

Five out of 10 evaluable patients with NSCLC experienced a partial response (PR), and another four had stable disease (SD), for a disease control rate (DCR) of 90 per cent (9/10).¹ All five patients with response to therapy had a treatment duration of 7.3-27.4 weeks at data cutoff and remain active on treatment. One patient with PR improved further to a complete response of the target lesions at week 18, post data cutoff.

In addition, 13 of 18 evaluable patients with CRC achieved SD, with the majority of CRC patients treated at the first two dose levels. Twenty-six patients remain on study and nine have discontinued.

Treatment-related adverse events (AEs) were primarily grade 1 events (approximately 68 per cent). Two grade 3 treatment-related AEs were reported (anemia and diarrhea). No grade 4 treatment-related AEs and no serious treatment-related AEs were reported. Enrollment into dose expansion is underway.

"While there's been significant progress in treating solid tumour cancers overall with targeted therapies, patients with the KRAS^G12C mutation have not benefited from these advances," said Marwan G. Fakih, M.D., clinical study investigator and co-director of the Gastrointestinal Cancer Program, City of Hope, Duarte, Calif. "In this early Phase 1 trial, investigational AMG 510 showed anti-tumour activity. We look forward to further investigating AMG 510 with the goal of closing the treatment gap for patients with this type of mutation."

About KRAS

The subject of more than three decades of research, the RAS gene family are the most frequently mutated oncogenes in human cancers.^2,3 Within this family, KRAS is the most prevalent variant and is particularly common in solid tumours.³ A specific mutation known as KRAS^G12C accounts for approximately 13 per cent of non-small cell lung cancers, three to five per cent of colorectal cancers and one to two per cent of numerous other solid tumours.⁴ Amgen is exploring the potential of KRAS^G12C inhibition across a broad variety of tumour types.

About Amgen Canada

As a leader in innovation, Amgen Canada understands the value of science. With main operations located in Mississauga, Ont.'s vibrant biomedical cluster, and its research facility in Burnaby, B.C., Amgen Canada has been an important contributor to advancements in science and innovation in Canada since 1991. The company contributes to the development of new therapies and new ways of using existing medicines in partnership with many of Canada's leading health-care, academic, research, government and patient organizations. To learn more about Amgen Canada, visit www.amgen.ca.

Forward-Looking Statements

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References

1.	Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). European Journal of Cancer. 2009;45:228-247.
2.	Cox A, et al. Drugging the undruggable RAS: Mission Possible? Nature Reviews Drug Discovery. 2014;13(11):828-851.
3.	Fernandez-Medarde A, Santos E. Ras in Cancer and Developmental Diseases. Genes Cancer. 2011;2(3):344-358.
4.	Lipford, JR. Pre-clinical development of AMG 510: the first inhibitor of KRASG12C in clinical testing. Oral presentation at AACR 2019; Atlanta, GA. March 29-April 3, 2019.

SOURCE Amgen Canada

Natasha Bond, Head of Corporate Affairs, Amgen Canada, 905-285-3007, [email protected]