Amgen Announces New Clinical Data Evaluating Novel Investigational KRAS(G12C) Inhibitor In Patients With Solid Tumors At ESMO 2019
The study enrolled 76 patients with KRAS G12C-mutant solid tumors. Data being presented at
"KRAS is the most frequently mutated oncogene in human tumors. Although KRASG12C has been a formidable target for nearly four decades, we can now report responses in patients with non-small cell lung, colorectal and appendiceal cancers," said
Among the 76 patients enrolled across treatment groups, 52 remain on treatment. The majority of treatment-related adverse events (TRAEs) were grade 1 and 2. Only two TRAEs were grade 3 (diarrhea and anemia). There were no grade 4 or higher TRAEs.
"The prognosis for patients with advanced colorectal cancer remains poor," said
About the Phase 1 Study
The Phase 1, first-in-human, open-label multicenter study enrolled patients with KRAS G12C- mutant solid tumors. Eligible patients were heavily pretreated with at least two or more prior lines of treatment, consistent with their tumor 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.
When evaluating tumor response, a partial response was defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as at least a 30% decrease in the sum of the diameters of target lesions.1 Stable disease was defined as having neither sufficient tumor shrinkage to qualify for a partial response nor sufficient increase to qualify for progressive disease.
The subject of almost four 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 tumors.3 A specific mutation known as KRAS G12C is found in approximately 13% of non-small cell lung cancers, three to five percent of colorectal cancers and one to two percent of numerous other solid tumors.4 Approximately 30,000 patients are diagnosed each year in
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- 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.
- Cox A, et al. Drugging the undruggable RAS: Mission possible? Nat Rev Drug Discov. 2014 Nov;13(11):828-51.
- Fernandez-Medarde A, Santos E. Ras in Cancer and Developmental Diseases. Genes Cancer. 2011 Mar;2(3):344-58.
- 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. Stephen AG, et al. Dragging ras back in the ring. Cancer Cell. 2014 Mar 17;25(3):272-81.
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