LUMAKRAS®/LUMYKRAS® (SOTORASIB) DEMONSTRATES SUPERIOR PROGRESSION-FREE SURVIVAL OVER DOCETAXEL IN FIRST POSITIVE PHASE 3 TRIAL OF A KRAS G12C INHIBITOR IN NON-SMALL CELL LUNG CANCER
At 1-Year, Progression-Free Survival was 25% for LUMAKRAS Versus 10% for Docetaxel
LUMAKRAS Met Key Secondary Endpoint of Objective Response Rate
LUMAKRAS Showed Clinically Meaningful Improvements in Patient-Reported Outcomes Compared to Docetaxel
"The totality of evidence from this study supports LUMAKRAS as an important targeted treatment option for patients with non-small cell lung cancer who harbor the KRAS G12C mutation, and reinforces the critical need for comprehensive biomarker testing for all patients with advanced disease," said
LUMAKRAS significantly improved PFS as determined by Blinded Independent Central Review (BICR) compared to docetaxel in heavily pre-treated patients (median PFS of 5.6 vs 4.5 months respectively; HR, 0.66 [95% CI: 0.51, 0.86]; P = 0.002). PFS favored LUMAKRAS across all clinically relevant subgroups, including those with a history of brain metastases at baseline. The proportion of patients with PFS at one year was 25% for LUMAKRAS versus 10% for docetaxel.
LUMAKRAS demonstrated a significantly higher ORR than docetaxel with double the response rates in the LUMAKRAS arm (28% versus 13%, respectively; P < 0.001) and showed consistent benefit across other efficacy secondary endpoints, specifically improved disease control rate (DCR; 83% versus 60%, respectively); faster time to response (TTR; 1.4 versus 2.8 months, respectively); and longer duration of response (DOR; 8.6 versus 6.8 months, respectively). Overall survival (OS; a key secondary endpoint) was not significantly different between treatment arms (10.6 versus 11.3 months, respectively; HR, 1.01 [95% CI: 0.77, 1.33]; P = 0.53). The study was not powered to detect a statistical difference in OS, and more than one-third of patients on docetaxel went on to receive a KRASG12C inhibitor, either in protocol cross-over (26.4%) or as subsequent therapy (7.5%). A clinically meaningful improvement in patient reported outcomes was also observed with LUMAKRAS versus docetaxel. Change over time (improvement from baseline to week 12) in global health status, physical functioning and dyspnea favored LUMAKRAS. Time to deterioration (delaying symptoms from getting worse) in global health status, physical functioning and cancer-related symptoms (dyspnea and cough) were delayed with LUMAKRAS compared to docetaxel.
There were fewer treatment-related adverse events (TRAEs) for LUMAKRAS versus docetaxel. Grade ≥ 3 TRAEs (33% LUMAKRAS; 40% docetaxel) and serious TRAEs (11% LUMAKRAS; 23% docetaxel) were lower with LUMAKRAS compared to docetaxel. The most common TRAEs reported by at least 15% of patients in either treatment group were diarrhea (34% LUMAKRAS; 19% docetaxel), fatigue (7% LUMAKRAS; 25% docetaxel), alopecia (1% LUMAKRAS; 21% docetaxel), nausea (14% LUMAKRAS; 20% docetaxel) and anemia (3% LUMAKRAS; 18% docetaxel).
"This is the first Phase 3 randomized clinical trial for a KRASG12C inhibitor to show benefit in heavily pre-treated patients who have limited treatment options," said
Data from CodeBreaK 200 will be submitted to global regulatory authorities where LUMAKRAS/LUMYKRAS has accelerated approval or conditional marketing authorization. LUMAKRAS is the only KRASG12C inhibitor approved anywhere in the world with approval in 44 markets, including
*This press release was initially issued on Sunday, Sept. 11 at 6:05pm Eastern Daylight Time (EDT) and was updated on Monday, Sept. 12 at 12:30pm EDT to include additional data following the ESMO presentation.
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 KRASG12C 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 KRASG12C inhibitor development program with unparalleled speed and exploring more than 10 sotorasib combination regimens, with clinical trial sites spanning five continents. To date, over 6,500 patients around the world have received LUMAKRAS/LUMYKRAS through the clinical development program and commercial use.
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 8% 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) enrolled 62 patients 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 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.
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
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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.
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CONTACT: Amgen, Thousand Oaks
LUMAKRAS and LUMYKRAS are trademarks of Amgen Inc.
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11 ClinicalTrials.gov. CodebreaK 200. Available at: https://clinicaltrials.gov/ct2/show/NCT04303780. Accessed on April 14, 2022.
12 ClinicalTrials.gov. CodeBreaK 101. Available at: https://clinicaltrials.gov/ct2/show/NCT04185883 . Accessed on April 14, 2022.
13 ClinicalTrials.gov. CodeBreaK 201. Available at: https://clinicaltrials.gov/ct2/show/NCT04933695. Accessed on
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