AMGEN PRESENTS NEW LUMAKRAS® (SOTORASIB) CODEBREAK 200 CNS DATA AT ASCO 2023

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04 Jun, 2023, 08:00 ET

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LUMAKRAS ® (sotorasib) Demonstrated Delayed Time to CNS Progression, Longer CNS PFS and Higher Intracranial ORR vs Docetaxel in Post-Hoc Analysis of Phase 3 CodeBreaK 200 Trial

LUMAKRAS Shows Improved PFS vs Docetaxel Across Key Co-Alteration Subgroups in the Phase 3 CodeBreaK 200 Study

LUMAKRAS Plus Vectibix® (panitumumab) and FOLFIRI Combination Show ORR of 55% in Previously Treated KRAS G12C-Mutated Metastatic CRC

THOUSAND OAKS, Calif., June 4, 2023 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the presentation of new data from the CodeBreaK clinical trial program, the most comprehensive global development program in patients with KRAS G12C-mutated cancers, at the American Society of Clinical Oncology (ASCO) Annual Meeting taking place June 2-6 in Chicago. The research presented reinforces the efficacy of LUMAKRAS®/LUMYKRAS® (sotorasib) in advanced non-small cell lung cancer (NSCLC) and metastatic colorectal cancer (mCRC). Additionally, data from SCARLET, an Amgen funded investigator study sponsored by the West Japan Oncology Group, will be presented on June 6 and is the first study to highlight the safety and efficacy of sotorasib in combination with platinum-based chemotherapy for frontline treatment of patients with advanced NSCLC harboring a KRAS G12C mutation.

"As the leader in KRAS inhibition, Amgen continues to advance the CodeBreaK program by evaluating LUMAKRAS across different indications and combinations to potentially help more people living with KRAS G12C-mutated cancers," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "These data presented at ASCO underscore the clinical importance of LUMAKRAS, including the only randomized trial of a KRASG12C inhibitor to show higher intracranial activity compared to chemotherapy, along with data validating our combination treatment approach in metastatic colorectal cancer, where new precision medicine strategies are desperately needed."

Improved CNS Activity in Advanced NSCLCIn the first and only randomized study for any KRASG12C inhibitor, data from a post-hoc analysis of the global Phase 3 CodeBreaK 200 trial included patients with advanced NSCLC and treated/stable central nervous system (CNS) lesions at baseline, as assessed by a blinded independent central review (BICR). In this analysis using a modified exploratory response assessment in neuro-oncology brain metastases (RANO-BM), LUMAKRAS demonstrated delayed time to CNS progression and longer CNS progression-free survival (PFS) compared with docetaxel.

Additionally, the CNS objective response rate (ORR),* an assessment of CNS tumor shrinkage following treatment, was more than double (33.3% vs 15.4%) in patients treated with LUMAKRAS (n= 18) compared to docetaxel (n= 13). The safety profile in this analysis was similar to the CodeBreaK 200 overall population.

"CNS metastases are an unfortunately common complication of KRAS G12C-mutated advanced NSCLC, occurring in about 30–40% of patients," said Melissa L. Johnson, M.D., director of Lung Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology. "In this post-hoc analysis from CodeBreaK 200, sotorasib delayed CNS progression-free survival by more than five months and is a potential clinically meaningful benefit for second-line NSCLC patients with KRAS G12C mutations."

These results will be presented on Sunday, June 4, as a late-breaking abstract in a poster discussion session: Lung Cancer—Non-Small Cell Metastatic, beginning at 4:30 p.m. CDT. (#LBA9016).

*Exploratory post-hoc analysis in patients with stable/treated CNS lesions at baseline, in which measurable lesions were defined per study as CNS lesions ≥10 mm in diameter by BICR using modified RANO-BM Criteria

New NSCLC Biomarker Data from CodeBreaK 200 Show Consistent Clinical Benefit Across SubgroupsIn the first randomized, molecularly-defined analysis of a KRASG12C inhibitor versus chemotherapy, LUMAKRAS showed improved PFS over docetaxel, irrespective of PD-L1 expression level, and retained PFS benefit versus docetaxel across key co-alteration subgroups (including STK11, KEAP1, TP53). Collectively, the biomarker data help inform treatment decision making and the ongoing CodeBreaK clinical development program, which explores LUMAKRAS in novel combinations.

These data will be presented on Tuesday, June 6 during an oral abstract session: Lung Cancer–Non-Small Cell Metastatic, from 9:45 a.m.- 12:45 p.m. CDT (Abstract #9008).

Encouraging Safety and Efficacy in Metastatic CRCData from the CodeBreaK 101 Phase 1B study, the first reported results for the combination of LUMAKRAS with Vectibix® (panitumumab) and FOLFIRI, showed encouraging safety and efficacy in previously-treated KRAS G12C-mutated metastatic CRC.

Among 42 patients evaluable for response, confirmed ORR was 55% (95% CI: 38.7, 70.2), and disease control rate (DCR) was 93% (95% CI: 80.5, 98.5), with responses observed regardless of the number of prior lines of therapy and regardless of progression on prior irinotecan-based therapy. LUMAKRAS plus Vectibix and FOLFIRI combination reported adverse events consistent with those expected for the therapies under study.

"A priority in KRAS G12C-mutated colorectal cancer research is exploring new treatment combinations that can drastically improve response rates attained with current treatments, which can be as low as 2%," said lead investigator, David S. Hong, M.D., professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, Houston. "These results showed encouraging efficacy with sotorasib in combination with panitumumab and FOLFIRI, and importantly showed consistent safety for each product."

These data will be presented on Monday, June 5 during a poster discussion session: Gastrointestinal Cancer—Colorectal and Anal, from 1:15-2:45 p.m. CDT (Abstract #3513.)

More information on Amgen's abstracts is available on the ASCO website.

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.i 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.ii

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.

In May 2021, LUMAKRAS was the first KRASG12C 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, Qatar, and in Australia, Brazil, Canada, Great Britain, Singapore, and Israel under the FDA's Project Orbis. Additionally, Amgen has submitted MAAs in Argentina, Colombia, Kuwait, Macao, Malaysia, Mexico, Russia, Saudi Arabia, Thailand and Turkey.

LUMAKRAS/LUMYKRAS is also being studied in multiple other solid tumors.iii

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.iv 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.v

KRAS G12C is the most common KRAS mutation in NSCLC.vi About 13% of patients with NSCLC harbor the KRAS G12C mutation.[vii] 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.viii

About Advanced Colorectal Cancer and the KRAS G12C Mutation

Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide, comprising 10% of all cancer diagnoses.ix It is also the third most commonly diagnosed cancer globally.x

Patients with previously treated metastatic CRC need more effective treatment options. For patients in the third-line setting, standard therapies yield median PFS times of about two months and patients' response rates are less than 2%.xi,xii

KRAS mutations are among the most common genetic alterations in colorectal cancers, with the KRAS G12C mutation present in approximately 3-5% of colorectal cancers.xiii,xiv,xv

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.xvi 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.ii The Phase 2 trial in metastatic colorectal cancer (mCRC) is fully enrolled and results have been published.xvii

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.xviii

Amgen also has several Phase 1b studies investigating sotorasib monotherapy and sotorasib combination therapy across various advanced solid tumors (CodeBreaK 101) open for enrollment.xix 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).xx

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

Interstitial Lung Disease (ILD)/Pneumonitis

Most Common Adverse Reactions

Drug Interactions

Please see LUMAKRAS full Prescribing Information. 

About Vectibix® (panitumumab)

Vectibix is the first fully human monoclonal anti-EGFR antibody approved by the FDA for the treatment of mCRC. Vectibix was approved in the U.S. in September 2006 as a monotherapy for the treatment of patients with EGFR-expressing mCRC after disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.

In May 2014, the FDA approved Vectibix for use in combination with FOLFOX, as first-line treatment in patients with wild-type KRAS (exon 2) mCRC. With this approval, Vectibix became the first-and-only biologic therapy indicated for use with FOLFOX, one of the most commonly used chemotherapy regimens, in the first-line treatment of mCRC for patients with wild-type KRAS mCRC.

In June 2017, the FDA approved a refined indication for Vectibix for use in patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) mCRC.

INDICATION AND LIMITATION OF USE

Vectibix® is indicated for the treatment of patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC): as first-line therapy in combination with FOLFOX, and as monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.

Limitation of Use: Vectibix® is not indicated for the treatment of patients with RAS mutant mCRC or for whom RAS mutation status is unknown.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: DERMATOLOGIC TOXICITY

Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients receiving Vectibix monotherapy [see Dosage and Administration (2.3), Warnings and Precautions (5.1), and Adverse Reactions (6.1)].

To see the Vectibix® Prescribing Information, including Boxed Warning, visit www.vectibix.com.

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.

Amgen Forward-Looking Statements

This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd., Kyowa-Kirin Co., Ltd., or any collaboration to manufacture therapeutic antibodies against COVID-19), the performance of Otezla® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), the Five Prime Therapeutics, Inc. acquisition, the Teneobio, Inc. acquisition, the ChemoCentryx, Inc. acquisition, or the proposed acquisition of Horizon Therapeutics plc, as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems such as the ongoing COVID-19 pandemic on our business, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

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 U.S. government, we could become subject to significant sanctions. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, such as COVID-19, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. A breakdown, cyberattack or information security breach could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all.

The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by the U.S. Food and Drug Administration, and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates. Further, any scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the U.S. Food and Drug Administration for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses.

CONTACT: Amgen, Thousand OaksMichael Strapazon, 805-313-5553 (media)Jessica Akopyan, 805-440-5721 (media)Arvind Sood, 805-447-1060 (investors)

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i Canon J, et al. Nature. 2019;575: 217–223.ii Skoulidis F, et al. N Engl J Med. 2021;384:2371-2381.iii Hong DS, et al. N Engl J Med. 2020;383:1207-1217.iv Sung H, et al. CA Cancer J Clin. 2021;71:209-249.v American Cancer Society. Lung Cancer Survival Rates. 2023. Available at: https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/survival-rates.html. Accessed on June 2, 2023.vi Arbour KC, et al. Clin Cancer Res. 2018;24:334-340.vii Nassar AF, et al. N Engl J. Med. 2021;384:185-187.viii Spira Al, et al. Lung Cancer. 2021;159:1-9.ix Rawla, P, et al. Gastroenterology Review. 2019;14(2):89-103.x World Health Organization. 2022 Statistics. Available at: https://www.who.int/en/news-room/fact-sheets/detail/cancer. Accessed on June 2, 2023.xi Mayer RJ, et al. N Engl J Med. 2015;372(20):1909-1919.xii Grothey A, et al. Lancet. 2013;381(9863):303-312.xiii Neumann J, et al. Pathol Res Pract. 2009;205(12):858-862.xiv Jones RP, et al. Br J Cancer. 2017;116(7):923-929.xv Wiesweg M, et al. Oncogene. 2019;38(16):2953-2966.xvi ClinicalTrials.gov. CodeBreaK 100. 2023. Available at: https://clinicaltrials.gov/ct2/show/NCT03600883. Accessed on June 2, 2023.xvii Fakih MG, et al. Lancet Oncol. 2022;23:115-124.xviii ClinicalTrials.gov. CodebreaK 200. 2023. Available at: https://clinicaltrials.gov/ct2/show/NCT04303780. Accessed on June 2, 2023.xix ClinicalTrials.gov. CodeBreaK 101. 2023. Available at: https://clinicaltrials.gov/ct2/show/NCT04185883. Accessed on June 2, 2023.xx ClinicalTrials.gov. CodeBreaK 201. 2023. Available at: https://clinicaltrials.gov/ct2/show/NCT04933695. Accessed on June 2, 2023.

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