Amgen (NASDAQ: AMGN) today announced that the European Commission (EC) has granted conditional marketing authorization for LUMYKRAS® (sotorasib), a first-in-class KRASG12C inhibitor, for the treatment of adults with advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation and who have progressed after at least one prior line of systemic therapy. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
“The approval of LUMYKRAS, the first and only targeted therapy for KRAS G12C-mutated NSCLC with proven efficacy, has the potential to transform treatment outcomes for people in the European Union living with this notoriously difficult-to-treat cancer,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “Amgen’s landmark scientific discovery allowed investigators to advance the first KRASG12C inhibitor into the clinic, and we look forward to bringing this critical innovation to more patients across the globe.”
The EC decision follows the recommendation for approval by the Committee for Medicinal Products for Human Use (CHMP) and is based on the positive results from the Phase 2 CodeBreaK 100 clinical trial in NSCLC, the largest trial conducted to date for patients with the KRAS G12C mutation. LUMYKRAS 960 mg, administered orally once-daily, demonstrated an objective response rate of 37.1% (95% CI: 28.6-46.2) and a median duration of response (DoR) of 11.1 months. The most common adverse reactions were diarrhea (34%), nausea (25%), and fatigue (21%). The most common severe (grade ≥ 3) adverse reactions were increased alanine aminotransferase level (ALT; 5%), increased aspartate aminotransferase (AST; 4%), and diarrhea (4%).
NSCLC accounts for approximately 84% of the 2.2 million new lung cancer diagnoses globally each year, including approximately 400,000 new cases in Europe 1,2 KRAS G12C is one of the most prevalent driver mutations in NSCLC, with about 13-15% of European patients with non-squamous NSCLC having the KRAS G12C mutation.3,4 With EC approval, and subject to local reimbursement applications, clinicians in all European Union member countries, as well as Norway, Iceland, and Liechtenstein, will be able to offer LUMYKRAS to appropriate patients with NSCLC.
About LUMAKRAS®/LUMYKRAS® (sotorasib)
Amgen took on one of the toughest challenges of the last 40 years in cancer research by developing LUMAKRAS/LUMYKRAS, a KRASG12C inhibitor.5 LUMAKRAS/LUMYKRAS has demonstrated a positive benefit-risk profile with rapid, deep and durable anticancer activity in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation with a once daily oral formulation.6
Amgen is progressing the largest and broadest global KRASG12C inhibitor development program with unparalleled speed and exploring more than 10 sotorasib combination regimens, including triplets, with clinical trial sites spanning five continents. To date, over 4,000 patients around the world have received LUMAKRAS/LUMYKRAS through the clinical development program and commercial use.
In May 2021, LUMAKRAS was the first KRASG12C inhibitor to receive regulatory approval anywhere in the world with its approval in the U.S., under accelerated approval.
Regulatory approvals have also been received in the United Arab Emirates (LUMAKRAS), Switzerland (LUMYKRAS), and under the FDA’s Project Orbis in Canada (LUMAKRAS) and Great Britain (LUMYKRAS). Through Project Orbis, Amgen also has Marketing Authorization Applications (MAAs) for sotorasib in review in Australia, Brazil, Singapore and Israel. Additionally, Amgen has submitted MAAs in Japan, South Korea, Turkey, Taiwan, Colombia, Thailand, Mexico, Hong Kong, Saudi Arabia, Argentina, Kuwait and Qatar.
LUMAKRAS/LUMYKRAS is also being studied in multiple other solid tumors.7
About Non-Small Cell Lung Cancer and the KRAS G12C Mutation
Lung cancer is the leading cause of cancer-related deaths worldwide, and it accounts for more deaths worldwide than colon cancer, breast cancer and prostate cancer combined.8 Overall survival rates for NSCLC are improving but remain poor for patients with advanced disease and 5-year survival is only 7% for those with metastatic disease.9
KRAS G12C is the most common KRAS mutation in NSCLC.10 About 13% of patients with non-squamous NSCLC harbor the KRAS G12C mutation.4 Unmet medical need remains high and treatment options are limited for NSCLC patients with the KRAS G12C mutation whose first-line treatment has failed to work or has stopped working. The outcomes with current therapies are suboptimal with a median progression-free survival of approximately 4 months following second-line treatment of KRAS G12C-mutated NSCLC.11
The CodeBreaK clinical development program for Amgen’s drug sotorasib is designed to study patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers.
CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumors.11 Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumor 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.7 The Phase 2 trial in colorectal cancer (CRC) is fully enrolled and results have been submitted for publication.12
CodeBreaK 200, the global Phase 3 randomized active-controlled study comparing sotorasib to docetaxel in KRAS G12C-mutated NSCLC completed enrollment of 345 patients. Eligible patients had previously treated, locally-advanced and unresectable or metastatic KRAS G12C-mutated NSCLC. The primary endpoint is progression-free survival and key secondary endpoints include overall survival, objective response rate, and patient-reported outcomes.
Amgen also has several Phase 1b studies investigating sotorasib monotherapy and sotorasib combination therapy across various advanced solid tumors (CodeBreaK 101) open for enrollment. A Phase 2 randomized study will evaluate sotorasib in patients with stage IV KRAS G12C-mutated NSCLC in need of first-line treatment (CodeBreaK 201).
About Amgen Oncology
At Amgen Oncology, our mission to serve patients drives all that we do. That’s why we’re relentlessly focused on accelerating the delivery of medicines that have the potential to empower all angles of care and transform lives of people with cancer.
For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company’s history, moving with great speed to advance those innovations for the patients who need them.