Long-Term Clinical Benefit and Prolonged Tumor Response Seen With 40.7% Objective Response Rate
No New Safety Signals Observed
Longest Follow-Up of Patients Treated With a KRAS G12C Inhibitor
Amgen (NASDAQ: AMGN) today announced the presentation of long-term efficacy and safety data from the CodeBreaK 100 Phase 12 trial in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) who received LUMAKRAS ® (sotorasib)*. The two-year follow-up data will be presented orally as part of a clinical trials plenary session at the American Association for Cancer Research (AACR) annual meeting on April 10, 2022 . LUMAKRAS is the first and only KRAS G12C inhibitor to-date to show long-term clinical benefit and overall survival in patients with NSCLC harboring the KRAS G12C mutation.
"With regulatory approvals in nearly 40 countries and thousands of patients treated, LUMAKRAS, the only approved KRAS G12C inhibitor, is a transformative targeted therapy for the treatment of patients living with KRAS G12C-mutated NSCLC," said David M. Reese , M.D., executive vice president of Research and Development at Amgen. "We are pleased with these latest results from the CodeBreaK 100 study, which represent the longest follow-up of patients treated with a KRAS G12C inhibitor and confirm rapid, deep and durable responses in patients receiving LUMAKRAS."
In this long-term, two-year analysis of 174 heavily pre-treated patients (172 with baseline measurable lesion(s)), LUMAKRAS demonstrated a centrally confirmed objective response rate (ORR) of 40.7%, disease control rate (DCR) of 83.7% and median duration of response (DOR) of 12.3 months. Five patients achieved complete responses and 65 patients achieved partial responses. The results also showed median progression-free survival (PFS) of 6.3 months and overall survival (OS) of 12.5 months with 32.5% of patients still alive at two years. No new safety signals for LUMAKRAS were identified with the long-term follow-up.
"Since the FDA approval almost a year ago, LUMAKRAS has changed the treatment paradigm for patients with advanced non-small cell lung cancer who harbor the KRAS G12C mutation," said Grace Dy , M.D., chief, thoracic oncology, Roswell Park Comprehensive Cancer Center. "The durable efficacy and positive benefit-risk profile seen in the two-year analysis of CodeBreaK 100 highlight the important role this innovative targeted therapy can offer long-term."
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 is now approved in 39 countries.
*LUMAKRAS is marketed as LUMYKRAS ® (sotorasib) in the European Union, the United Kingdom and Switzerland .
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
Amgen is progressing the largest and broadest global KRAS G12C 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 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 and Switzerland and in Australia , Brazil , Canada , and Great Britain under the FDA's Project Orbis. Through Project Orbis, Amgen also has Marketing Authorization Applications (MAAs) for sotorasib in review in Israel and Singapore . Additionally, Amgen has submitted MAAs in Argentina , Colombia , Hong Kong , Kuwait , Malaysia , Mexico , Qatar , Saudi Arabia , Taiwan , Thailand and Turkey .
LUMAKRAS/LUMYKRAS is also being studied in multiple other solid tumors. 3
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. 4 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. 5
KRAS G12C is the most common KRAS mutation in NSCLC. 6 About 13% of patients with NSCLC harbor the KRAS G12C mutation. 7 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. 8
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. 9 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 colorectal cancer (CRC) is fully enrolled and results have been published. 10
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. 11
Amgen also has several Phase 1b studies investigating sotorasib monotherapy and sotorasib combination therapy across various advanced solid tumors (CodeBreaK 101) open for enrollment. 12 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). 13
For information, please visit www.hcp.codebreaktrials.com .
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
- 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 ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and cough.
- 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 H 2 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.
At Amgen, we're advancing oncology at the speed of life ™ .
For more information, follow us on www.twitter.com/amgenoncology .
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 2021, Amgen was named one of the 25 World's Best Workplaces™ by Fortune and Great Place to Work™ and one of the 100 most sustainable companies in the world by Barron's .
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CONTACT: Amgen, Thousand Oaks
Megan Fox , 805-447-1423 (media)
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LUMAKRAS, LUMYKRAS, Otezla, and Advancing Oncology at The Speed of Life are trademarks of Amgen Inc.
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