Benzinga | Nov 12, 2021 07:36AM EST

Amgen Reports Positive European Medicines Agency Committee For Medicinal Products For Human Use For LUMYKRAS For Patients With KRAS G12C-Mutation

First Targeted Therapy for the KRAS G12C Mutation Recommended for Approval in the European Union

Positive Opinion Based on Clinical Results Demonstrating Durable Responses and a Favorable Benefit-Risk Profile With LUMYKRAS

KRAS G12C Mutation Shown to be Present in Approximately 13-15% of Patients in Europe With NSCLC[1],[2]

THOUSAND OAKS, Calif., Nov. 12, 2021 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending conditional marketing authorization of LUMYKRAS(r) (sotorasib), known as LUMAKRAS(r) in the U.S., 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. If the European Commission follows the recommendation for approval, LUMYKRAS will be the first targeted therapy available in the European Union (EU) for the KRAS G12C mutation, one of the most prevalent biomarkers in NSCLC.

"After 40 years of cancer research to target the KRAS mutation, many in the scientific community believed that KRAS was 'undruggable' leaving patients with this mutation with limited treatment options," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "The LUMYKRAS development program was designed to bring this targeted therapy to patients with KRAS G12C-mutated non-small cell lung cancer as quickly as possible. The EMA CHMP positive opinion brings patients in the EU closer to this transformative therapy and highlights our commitment to improving patient outcomes in difficult-to-treat cancers."

The CHMP based its positive opinion on results from the Phase 2 CodeBreaK 100 clinical trial, the largest trial conducted to date exclusively for patients with the KRAS G12C mutation. CodeBreaK 100 enrolled 126 patients, 124 of whom had centrally evaluable lesions at baseline. In the trial, LUMYKRAS demonstrated favorable efficacy and tolerability in these 124 patients with KRAS G12C mutation-positive NSCLC who had disease progression after receiving an immunotherapy and/or chemotherapy. LUMYKRAS 960 mg, administered orally once-daily, demonstrated an objective response rate (a proportion of patients with ? 30% decrease in the sum of the longest diameter of the target lesions compared with baseline) of 37.1% (95% CI: 28.6-46.2) a median duration of response (DoR) of 11.1 months, disease control rate (DCR) of 80.6% and median overall survival (OS) of 12.5 months.3

The most common treatment-related adverse reactions were diarrhea (32%), nausea (19%), increase in aminotransferase level (ALT) and increase in the aspartate aminotransferase level (AST) (15% each). The most common severe (grade ? 3) treatment-related adverse reactions were increased alanine aminotransferase (ALT; 6%), increased aspartate aminotransferase (AST; 6%), and diarrhea (4%). Only 7% of patients discontinued treatment due to treatment-related adverse events.3

The detailed CodeBreaK 100 Phase 2 data in NSCLC were presented at the 2020 World Conference on Lung Cancer (WCLC) and published in the New England Journal of Medicine (NEJM).

"Patients with KRAS G12C-mutated NSCLC face poor prognosis and usually do not respond to currently available treatments," said Prof. Fabrice Barlesi, general director of Gustave Roussy, Villejuif, France. "The introduction of sotorasib in the EU as a novel treatment option would be a welcome development as a potentially new standard of care for the tens of thousands of patients with NSCLC living with this common mutation."

"The rapid tumor shrinkage and durable responses observed in the large-scale CodeBreaK 100 clinical trial that support this positive opinion are impressive and demonstrate the potential benefit sotorasib can offer our patients who have the KRAS G12C mutation," said Prof. J?rgen Wolf, M.D., medical director, Center for Integrated Oncology, University Hospital of Cologne, Germany. "As we move closer to a potential EMA approval, it is critical that we continue to increase the implementation of biomarker testing so we can match the right patients who may benefit from this first-in-class targeted therapy as quickly as possible."

NSCLC accounts for approximately 84% of the 2.2 million new lung cancer diagnoses each year worldwide, including approximately 400,000 new cases in Europe.4,5 KRAS G12C is one of the most prevalent driver mutations in NSCLC, with about 13-15% of patients with non-squamous NSCLC having the KRASG12C mutation.6,7 LUMYKRAS, which is administered orally in a tablet formulation, binds with the mutated KRAS G12C protein keeping the mutated protein in an inactive state, thus preventing it from switching to its favored active state that supports cancer cell growth. LUMYKRAS has been shown to irreversibly bind to the inactive KRAS G12C protein, permanently locking it in an inactive state, inhibiting oncogenic signaling and tumorigenesis.3,8

The CHMP's recommendation will now be reviewed by the European Commission, which has the authority to approve medicines for use throughout the European Union. A European Commission decision is expected by mid-January 2022.

In May 2021, LUMAKRAS(r) 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(tm)), and under Project Orbis in Canada (LUMAKRAS(tm)) and Great Britain (LUMYKRAS(r)). In addition to our EMA MAA, there are 16 regulatory applications pending review around the world.