Amgen Presents Results From Phase 2 Cohort of CodeBreaK 100 Clinical Study Evaluating Investigational Sotorasib in Patients with KRAS G12C-Mutated Advanced Non-Small Cell Lung Cancer (NSCLC)
The results are the first from a completed pivotal Phase 2 study in NSCLC
with a median follow-up of more than one year
MISSISSAUGA, ON, Feb. 1, 2021 /CNW/ - Amgen has announced results from the Phase 2 cohort of the CodeBreaK 100 clinical study evaluating investigational sotorasib (AMG 510) in 126 patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC). These results were presented during the Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer (WCLC) and are the first from a completed pivotal Phase 2 study in NSCLC with a median follow-up of more than one year. Please note the safety and efficacy of sotorasib is still under investigation and market authorization has not been obtained.
Sotorasib demonstrated a confirmed objective response rate (ORR) and disease control rate (DCR) in previously treated patients with KRAS G12C-mutated advanced NSCLC. The results were also consistent with earlier Phase 1 results. Patients were treated with sotorasib 960 mg once daily orally, Prior to the trial, 81 % of patients had progressed on platinum-based chemotherapy and PD1/L1 inhibitors, with the remainder progressing after having received one of these therapies.
"There remains a significant unmet need for new therapeutic options to help support patients with advanced non-small cell lung cancer who have failed first-line treatment," said Suna Avcil, executive medical director, Amgen Canada. "Scientists and researchers around the world have invested four decades of research into trying to find these answers. We are encouraged by the results of this Phase 2 study and believe they offer important clinical insights."
"I am pleased to see continued progress in the development of potential therapies for patients with advanced NSCLC harbouring a KRAS G12-C mutation," said Dr. Adrian G. Sacher, M.D., M.M.Sc., F.R.C.P.C., Division of Medical Oncology & Hematology Princess Margaret Cancer Centre. "This research is critical to better understanding the disease and, more importantly, moving toward better patient care."
Most treatment-related adverse events (TRAEs) associated with sotorasib were mild to moderate (grade 1 or 2) and no treatment-related deaths. Grade 3 TRAEs were reported in 25 (19.8%) patients and 1 patient (0.8%) reported a Grade 4 TRAE. The most frequently reported TRAEs (any grade) were diarrhea (31.0%), nausea (19.0%), increased alanine aminotransferase (15.1%) and increased aspartate aminotransferase (15.1%). TRAEs led to treatment discontinuation in 7.1% of patients.
NSCLC accounts for 80%-85% of all lung cancers, and most patients (66%) have advanced or metastatic disease at initial diagnosis.1,2 KRAS G12C is one of the most common driver mutations in NSCLC3 and there is a high unmet need and poor outcomes associated in the second-line treatment of KRAS G12C driven NSCLC.4 Approximately 13 per cent of patients with NSCLC harbour the KRAS G12C mutation.5,6
Following recent regulatory submissions in the U.S., European Union, Australia, Brazil, Canada and UK, Amgen is working with regulatory agencies across the globe to bring sotorasib to NSCLC patients as quickly as possible. Amgen's request for sotorasib to be considered for accelerated review under the Notice of Compliance with conditions (NOC/c) pathway in Canada was recently determined to be acceptable.
Amgen has taken on one of the toughest challenges of the last 40 years in cancer research by developing sotorasib, an investigational KRASG12C inhibitor.7 Sotorasib was the first KRASG12C inhibitor to enter the clinic and is being studied in the broadest clinical program exploring 10 combinations with global sites spanning five continents. In just over two years, the sotorasib clinical program has established the largest clinical data set with more than 700 patients studied across 13 tumour types to date.
The CodeBreaK clinical development 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 2 study was centrally assessed objective response rate. The Phase 2 trial in NSCLC enrolled 126 patients, 124 of whom had centrally evaluable lesions by RECIST at baseline. The Phase 2 trial in colorectal cancer (CRC) is fully enrolled and topline results are expected in 2021.
A global Phase 3 randomized active-controlled study comparing sotorasib to docetaxel in patients with KRAS G12C-mutated NSCLC (CodeBreaK 200) is currently recruiting. Amgen also has more than 10 Phase 1b combination studies across various advanced solid tumours (CodeBreaK 101) open for enrollment.
For information, please visit 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 healthcare, 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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|1 American Cancer Society. https://www.cancer.org/cancer/lung-cancer/about/what-is.html. Accessed January 2021.|
|2 Ahmadzada T, et al. J Clin Med. 2018;7:153.|
|3 Liu P, et al. Acta Pharmaceutica Sinica B. 2019;9(5):871–879.|
|4 Pakkala S, et al. JCI Insights. 2018;3:3120858|
|5 Biernacka A, et al. Cancer Genet. 2016;209:195-198.|
|6 Cox AD, et al. Nat Rev Drug Discov. 2014;13:828-851.|
|7 Canon J, et al. Nature. 2019;575:217-223.|
SOURCE Amgen Canada