THOUSAND OAKS, Calif., Aug. 21, 2023 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the U.S. 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 Oct. 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 program and commercial use.

Lumakras has demonstrated a favorable benefit/risk profile in multiple studies in non-small lung cancer and other tumor types such as colo-rectal cancer. Amgen is progressing the largest and broadest global KRAS^G12C inhibitor development program 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 Dec. 24, 2023, has been set.

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 KRAS^G12C inhibitor.¹ 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.²

In May 2021, LUMAKRAS was the first KRAS^G12C inhibitor to receive regulatory approval with its approval in the U.S., 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 tumors. 

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.³ 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.⁴

KRAS G12C is the most common KRAS mutation in NSCLC.⁵ About 13% of patients with NSCLC harbor the KRAS G12C mutation.⁶ 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.⁷

About CodeBreaK 

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.⁸ 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.² The Phase 2 trial in metastatic colorectal cancer (mCRC) enrolled 62 patients and results have been published.⁹

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.¹⁰

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).¹¹

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.¹²  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).¹³

LUMAKRAS^® (sotorasib) U.S. Indication 

LUMAKRAS is indicated 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). 

LUMAKRAS^® (sotorasib) Important U.S. Safety Information 

Hepatotoxicity 

• LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
• Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.
• Monitor liver function tests (ALT, AST and total bilirubin) prior to the start of LUMAKRAS every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations.
• Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.

Interstitial Lung Disease (ILD)/Pneumonitis 

• LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100, ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients.
• Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified.

Most Common Adverse Reactions 

• The most common adverse reactions occurring in ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and cough.

Drug Interactions 

• Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, dietary and herbal products.
• Inform patients to avoid proton pump inhibitors and H₂ receptor antagonists while taking LUMAKRAS.
• If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid.

Please see LUMAKRAS full Prescribing Information.  

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. 

For more information, follow us on www.twitter.com/amgenoncology. 

About Amgen 

Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology. 

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential. 

Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2022, Amgen was named one of the "World's Best Employers" by Forbes and one of "America's 100 Most Sustainable Companies" by Barron's.

For more information, visit Amgen.com and follow us on Twitter, LinkedIn, Instagram, TikTok and YouTube.

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CONTACT: Amgen, Thousand Oaks
Elissa Snook, 609-251-1407 (media)
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