Lumakras® (sotorasib) combined with Vectibix® (panitumumab) shows confirmed 30% objective response rate in patients with KRAS G12C-mutated metastatic colorectal cancer

Phase 1b Results Demonstrate Encouraging Median Progression-Free Survival of 5.7 Months in Difficult-to-Treat Patient Population

THOUSAND OAKS, CA, USA I September 12, 2022 I Amgen (NASDAQ: AMGN) today announced updated data from its Phase 1b CodeBreaK 101 study, one of the most comprehensive global clinical development programs in patients with KRAS G12C-mutated colorectal cancer (CRC). These data show that combining LUMAKRAS®/LUMYKRAS® (sotorasib) with Vectibix® (panitumumab), Amgen's monoclonal anti-epidermal growth factor receptor (anti-EGFR) antibody, demonstrated encouraging efficacy and safety. Overall, the confirmed objective response rate (ORR) was 30% in patients with chemo-refractory metastatic colorectal cancer (mCRC). These data were presented today during an oral session at the European Society for Medical Oncology (ESMO) Annual Meeting in Paris, France.

"We are thrilled to see these CodeBreaK 101 results, which show that LUMAKRAS plus Vectibix achieved a 30% confirmed objective response rate in patients with KRAS G12C-mutated metastatic colorectal cancer. Treatment response rates can be as low as 2% in this patient population, and the current standard of care offers a median progression-free survival benefit of two months, so developing new treatment options is critically important for patients," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "These data are encouraging as we continue to focus on combination approaches in colorectal cancer, including advancing CodeBreaK 300, the Phase 3 LUMAKRAS plus Vectibix trial in the chemotherapy-refractory patient population."

In total, 40 patients with heavily pre-treated (median of two prior lines of therapy; range 1-7) KRAS G12C-mutated chemo-refractory mCRC were enrolled in the dose expansion cohort for the combination of LUMAKRAS and Vectibix. Disease control was seen in 37 patients for a total of 92.5% with a median progression free survival (PFS) of 5.7 months. There were no apparent differences found in the efficacy between left-sided and right-sided tumors. Tumor shrinkage of any magnitude was observed in 88% of patients, based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and the median Duration of Treatment (DoT) was 5.9 months with 25% of patients remaining on treatment at the time of data cutoff. With a median follow up of 8.8 months, median overall survival (OS) was not yet reached. Treatment-related adverse events (TRAEs) reported with the combination were consistent with known safety profiles of the individual medicines, and no TRAEs resulted in discontinuation of either drug.

"These data are positive news for patients because they demonstrate encouraging efficacy and safety for sotorasib and panitumumab, as current treatments for chemo-refractory colorectal cancer provide limited survival benefits and can have notable safety issues," said Yasutoshi Kuboki, chief, Department of Experimental Therapeutics, National Cancer Center Hospital East, Japan. "There is a significant treatment gap for patients with KRAS G12C-mutated colorectal cancer and it is imperative that we continue to explore and develop precision therapies, like sotorasib, for these patients."

KRAS is a commonly mutated oncogene in CRC, with mutations in approximately 40% of all cases, with the KRAS G12C mutation present in approximately 3-5% of colorectal cancers. These patients face a dismal prognosis and have very limited treatment options.

*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 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. 

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.3 

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.4 It is also the third most commonly diagnosed cancer globally.5

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%.6,7

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. 8,9,10

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.11 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.12 

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.13 

Amgen also has several Phase 1b studies investigating sotorasib monotherapy and sotorasib combination therapy across various advanced solid tumors (CodeBreaK 101) open for enrollment.14 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).15 

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). 

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 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. 

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 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

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen

1 Canon J, et al. Nature. 2019;575: 217–223. 
2 Skoulidis F, et al. N Engl J Med. 2021;384:2371-2381. 
Hong DS, et al. N Engl J Med. 2020;383:1207-1217. 
4 Rawla, P., Sunkara, T., & Barsouk, A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Gastroenterology Review. 2019;14(2):89-103.
5 World Health Organization. 2020 Statistics. Available at: https://www.who.int/en/news-room/fact-sheets/detail/cancer. Accessed on August 26, 2021.
6 Mayer RJ, Van Cutsem E, Falcone A, et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015;372(20):1909-1919. doi:10.1056/NEJMoa1414325.
7 Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):303-312. doi:10.1016/S0140-6736(12)61900-X.
8 Neumann J, Zeindl-Eberhart E, Kirchner T, Jung A. Frequency and type of KRAS mutations in routine diagnostic analysis of metastatic colorectal cancer. Pathol Res Pract. 2009;205(12):858-862. doi:10.1016/j.prp.2009.07.010.
9 Jones RP, Sutton PA, Evans JP, et al. Specific mutations in KRAS codon 12 are associated with worse overall survival in patients with advanced and recurrent colorectal cancer. Br J Cancer. 2017;116(7):923-929. doi:10.1038/bjc.2017.37.
10 Wiesweg M, Kasper S, Worm K, et al. Impact of RAS mutation subtype on clinical outcome-a cross-entity comparison of patients with advanced non-small cell lung cancer and colorectal cancer. Oncogene. 2019;38(16):2953-2966. doi:10.1038/s41388-018-0634-0.
11 ClinicalTrials.gov. CodeBreaK 100. Available at: https://clinicaltrials.gov/ct2/show/NCT03600883. Accessed on April 14, 2022.
12Fakih MG, et al. Lancet Oncol. 2022;23:115-124.
13 ClinicalTrials.gov. CodebreaK 200. Available at: https://clinicaltrials.gov/ct2/show/NCT04303780. Accessed on April 14, 2022.
14 ClinicalTrials.gov. CodeBreaK 101. Available at: https://clinicaltrials.gov/ct2/show/NCT04185883. Accessed on April 14, 2022.
15 ClinicalTrials.gov. CodeBreaK 201. Available at: https://clinicaltrials.gov/ct2/show/NCT04933695. Accessed on April 14, 2022.

SOURCE: Amgen

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