FDA Approves LUMAKRAS™ (Sotorasib), The First And Only Targeted Treatment For Patients With KRAS G12C-Mutated Locally Advanced Or Metastatic Non-Small Cell Lung Cancer
To view the multimedia assets associated with this release, please click: https://www.multivu.com/players/English/8812853-amgen-fda-approval-lumakras-sotorasib-targeted-kras-g12c-lung-cancer/
"The FDA approval of LUMAKRAS is a breakthrough moment for patients with KRAS G12C-mutated non-small cell lung cancer because there is now a targeted therapy for this common, but previously elusive, mutation," said
The FDA approval of LUMAKRAS is based on results from a subset of patients in CodeBreaK 100, the largest clinical trial conducted to date exclusively for patients with the KRAS G12C mutation. The trial demonstrated favorable efficacy and tolerability in 124 patients with KRAS G12C mutation-positive NSCLC who had disease progression after receiving an immunotherapy and/or chemotherapy. In the trial, 960 mg of LUMAKRAS administered orally once-daily demonstrated an ORR (a proportion of patients with ≥ 30% decrease in tumor) of 36% (95% CI: 28-45) with 81% (95% CI: 73-87) of patients achieving disease control (percentage of patients who have achieved complete response, partial response and stable disease for more than three months). The median DoR was 10 months. The most common adverse reactions (≥ 20%) were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and cough. Adverse reactions resulting in permanent discontinuation of LUMAKRAS occurred in 9% of patients.
"Sotorasib represents a major advancement in oncology and changes the treatment paradigm for patients with KRAS G12C-mutated non-small cell lung cancer," said Bob
NSCLC accounts for approximately 84% of the 2.2 million new lung cancer diagnoses each year worldwide, including approximately 236,000 new cases in the
About half of all patients with NSCLC harbor a targetable driver mutation, yet despite the integral role that biomarkers play in identifying patients who may benefit from targeted therapies, many patients are not tested.4,5
"Biomarker testing for patients with non-small cell lung cancer is critical because it informs a patient's treatment path with a personalized and tailored approach. The only way to identify the KRAS G12C mutation is to test for it, so I urge patients to ask their care teams about comprehensive biomarker testing. It is important that patients and their healthcare providers know that KRAS G12C is now an actionable mutation," said Andrea Ferris, president and CEO of LUNGevity. "Today's FDA approval of a therapy targeted for KRAS G12C, one of the most prevalent biomarkers in non-small cell lung cancer, brings hope to the many patients who carry this mutation and is a significant moment for the lung cancer community who need more innovative treatment options."
Amgen to Webcast Investor Call on LUMAKRAS FDA Approval
Amgen will host a webcast call for the investment community on Tuesday, June 1, 2021 at 5 a.m. PT / 8 a.m. ET.
Live audio of the investor call will be simultaneously broadcast over the Internet and will be available to members of the news media, investors and the general public.
The webcast, as with other selected presentations regarding developments in Amgen's business given by management at certain investor and medical conferences, can be found on Amgen's website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen's Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.
About LUMAKRAS™ (sotorasib)
LUMAKRAS has demonstrated a positive benefit-risk profile with rapid, deep and durable anticancer activity in patients with locally advanced and metastatic non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation with a once daily oral formulation. As part of the evaluation for this accelerated approval, FDA is requiring a post-marketing trial to investigate whether a lower dose will have a similar clinical effect.
LUMAKRAS is also being studied in multiple other solid tumors.6
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 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 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 Non-Small Cell
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 7% for those with metastatic disease.7
KRAS G12C is the most common KRAS mutation in NSCLC.8 In the
The CodeBreaK clinical development program for Amgen's drug sotorasib is designed to treat patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers. As the most advanced KRAS G12C clinical development program, CodeBreaK has enrolled more than 800 patients across 13 tumor types since its inception.
CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumors. 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. The Phase 2 trial in colorectal cancer (CRC) is fully enrolled and topline results are expected later in 2021.
A global Phase 3 randomized active-controlled study comparing sotorasib to docetaxel in patients with KRAS G12C-mutated NSCLC (CodeBreaK 200) has completed enrollment.
For information, please visit www.hcp.codebreaktrials.com.
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,
For more information, follow us on www.twitter.com/amgenoncology.
This news release contains forward-looking statements that are based on the current expectations and beliefs of
No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints we have selected. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market.
Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the
CONTACT: Amgen, Thousand Oaks
Amgen. Data on File. 2020. American Cancer Society. Key Statistics for Lung Cancer. 2021. https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html. Accessed May 20, 2021.
- Sung H, et al. CA Cancer J Clin. 2021;71(3):209-249.
- Baumgart M. Am J Hematol Oncol. 2015;11:10-13.
- Gierman HJ, et al. J Clin Oncol. 2019;37(Suppl 15):Abstract 1585.
- Hong DS, et al. N Engl J Med. 2020;383:1207-1217.
American Cancer Society. Lung Cancer Survival Rates. 2021. https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/survival-rates.html. Accessed May 20, 2021.
- Arbour KC, et al.
Clin CancerRes. 2018;24(2):334-340.
- Aggarwal S, et al. Poster presentation at
ESMO Virtual Congress2020, Sep. 19-21, 2020. Poster 1339P.
View original content:http://www.prnewswire.com/news-releases/fda-approves-lumakras-sotorasib-the-first-and-only-targeted-treatment-for-patients-with-kras-g12c-mutated-locally-advanced-or-metastatic-non-small-cell-lung-cancer-301301808.html