Clinical Data From Full Phase 1 Cohort of Investigational Sotorasib Published in New England Journal of Medicine

NSCLC Data Featured in Proffered Presentation Session at Virtual ESMO 2020

Manuscript Represents First Phase 1 Results Published for a KRAS^G12C Inhibitor

MISSISSAUGA, ON, Sept. 22, 2020 /CNW/ - Amgen has announced that updated data from the full Phase 1 cohort of the CodeBreaK 100 clinical study, evaluating sotorasib (proposed INN for AMG 510) in 129 patients across multiple advanced solid tumours, were published in the New England Journal of Medicine (NEJM). Data from 59 patients with advanced non-small cell lung cancer (NSCLC) reported in the NEJM manuscript were also featured during an oral presentation at ESMO 2020. Please note the safety and efficacy of sotorasib is still under investigation and market authorization has not been obtained.

"We are pleased to present the updated Phase 1 results of CodeBreaK 100, the largest Phase 1/2, and first-in-human, clinical study for a KRAS^G12C inhibitor," said Dr. Suna Avcil, executive medical director, Amgen Canada. "This data, combined with data presented earlier this year, offers important insight into the development of therapeutic options for non-small cell lung cancer, advanced colorectal cancer, and other solid tumours."

A total of 59 patients with NSCLC were treated, of which 34 received the 960 mg daily dose (data cutoff of June 1, 2020). The data demonstrated confirmed objective response rate (ORR) and disease control rates (DCR) in these heavily pretreated patients.

Activity was seen across all dose levels in patients with NSCLC. Tumour shrinkage was assessed in patients at the first week-6 assessment. 

Tolerability in patients with NSCLC was consistent with previously seen CodeBreaK 100 results. No dose-limiting toxicities were observed and there were no fatal treatment-related adverse events (TRAEs). The most common TRAEs were diarrhea (25.4%), alanine aminotransferase (ALT) increase (20.3%), aspartate aminotransferase (AST) increase (20.3%), fatigue (10.2%) and nausea (10.2%). Eleven (18.6%) patients had grade 3 or higher TRAEs, one of whom had grade 3 TRAEs of ALT and AST increases that led to discontinuation of treatment.

"KRAS G12C is a driver mutation that is central to the biology of non-small cell lung cancer, colorectal cancer and other solid tumours. Historically, this mutation has been considered un-druggable" said Dr. Adrian G. Sacher, M.D., M.M.Sc., F.R.C.P.C., Division of Medical Oncology & Hematology Princess Margaret Cancer Centre. "These findings provide important insight into therapies that may target KRAS G12C in metastatic non-small cell lung cancer."  

The ESMO oral presentation included Phase 1 NSCLC results published in NEJM, as well as data on potential biomarkers of response to sotorasib that demonstrated clinical activity across a range of KRAS G12C mutant allele frequencies (MAFs), PD-L1 tissues expression levels, tumour mutational burden (TMB) plasma levels and tissue co-mutational profiles.

About KRAS
The RAS gene family, which has been the subject of almost four decades of research, contains some of the most frequently mutated oncogenes in human cancers.^[i],[ii] KRAS is the most prevalent variant within this gene family and is particularly common in solid tumours.  It also accounts for about 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, making this among the most broadly represented mutations across cancer patient subgroups.^{[v],[vi],[vii],[viii],[ix]}. With the discovery and exploitation of a unique surface groove in the KRAS^G12C protein, Amgen was able to advance the first investigational KRAS^G12C inhibitor into the clinic and is exploring the potential of KRAS^G12C inhibition across multiple tumour types.

About CodeBreaK
The CodeBreaK clinical trial program for Amgen's investigational drug sotorasib is designed to study patients with an advanced solid tumour with the KRAS G12C mutation.

CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumours. Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumour type and stage of disease. The primary endpoint for the Phase 1 study is safety, and key secondary endpoints include 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. 

Additional information about CodeBreaK clinical trials can be found at http://www.codebreaktrials.com.

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 and follow us on www.twitter.com/amgencanadagm.

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SOURCE Amgen Canada