US-FDA committee to review Amgen data supporting sNDA for full approval of Lumakras to treat KRAS G12C-mutated NSCLC

Amgen announced the US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) will review data supporting the supplemental New Drug Application (sNDA) for the full approval of Lumakras (sotorasib) for adults with previously treated locally advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC) at a meeting on October 5, 2023.

Lumakras/Lumykras is approved in several markets outside the United States including Europe, South America, Asia and the European Union. To date, over 6,500 patients around the world have received Lumakras/Lumykras through the clinical development programme and commercial use.

Lumakras has demonstrated a favourable benefit/risk profile in multiple studies in non-small lung cancer and other tumour types such as colo-rectal cancer. Amgen is progressing the largest and broadest global KRASG12C inhibitor development programme exploring multiple combination regimens, with clinical trial sites spanning five continents.

"We believe in the clinical value of Lumakras for prescribers and patients navigating KRAS G12C-mutated NSCLC and we look forward to discussing the comprehensive data package for Lumakras with members of the Committee," said David M. Reese, M.D., executive vice president of research and development at Amgen.

Lumakras received accelerated approval from the FDA on May 28, 2021. The sNDA for full approval of Lumakras was accepted by the FDA for standard review and a Prescription Drug User Fee Act (PDUFA) target action date of December 24, 2023, has been set.

Amgen took on one of the toughest challenges of the last 40 years in cancer research by developing Lumakras/Lumykras, a KRASG12C inhibitor. 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) harbouring the KRAS G12C mutation with a once daily oral formulation.

In May 2021, Lumakras was the first KRASG12C inhibitor to receive regulatory approval with its approval in the US, under accelerated approval. Lumakras/Lumykras is also approved in the European Union, Japan, United Arab Emirates, South Korea, Hong Kong, Switzerland, Taiwan, Turkey, Thailand, Qatar, Australia, Argentina, Brazil, Canada, Great Britain, Kuwait, Macao, Singapore, Mexico, Israel, Bulgaria, Hungary, Romania, and Russia. Additionally, Amgen has submitted MAAs in Colombia, Malaysia and Saudi Arabia.

Lumakras/Lumykras is also being studied in multiple other solid tumours.

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. Overall survival rates for NSCLC are improving but remain poor for patients with advanced disease, and 5-year survival is only 9% for those with metastatic disease.

KRAS G12C is the most common KRAS mutation in NSCLC. About 13% of patients with NSCLC harbour the KRAS G12C mutation. The 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 other approved therapies are suboptimal, with a median progression-free survival of approximately four months following second-line treatment of KRAS G12C-mutated NSCLC.

The CodeBreaK clinical development programme for?Amgen's drug sotorasib is designed to study patients with an advanced solid tumour 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 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 metastatic colorectal cancer (mCRC) enrolled 62 patients and results have been published.

CodeBreaK 200, the global phase 3 multicenter, randomized, open-label, active-controlled study compared the efficacy, safety, and tolerability of 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 was progression-free survival and key secondary endpoints included overall survival, objective response rate, and patient-reported outcomes.

CodeBreaK 300, the global phase 3 randomized active-controlled study comparing sotorasib in combination with panitumumab to investigator's choice (trifluridine and tipiracil, or regorafenib) in chemorefractory KRAS G12C-mutated mCRC, has completed enrollment of 160 patients. Eligible patients had KRAS G12C-mutated mCRC, received at least one prior line of therapy, and have received and progressed on or after fluoropyrimidine, irinotecan, and oxaliplatin. The primary endpoint is progression-free survival and key secondary endpoints include overall survival (OS) and objective response rate (ORR).

Amgen also has several phase 1b studies investigating sotorasib in combination with several other treatments across various advanced solid tumors (CodeBreaK 101) open for enrollment.  A phase 3 randomized controlled study will evaluate frontline sotorasib in combination with platinum doublet chemotherapy versus pembrolizumab platinum doublet combination in patients with PD-L1-negative, advanced KRAS G12C-mutated NSCLC (CodeBreaK 202).

Lumakras?is indicated in US for the treatment of adult patients with?KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

At?Amgen?Oncology, its 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.

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