Lumakras (sotorasib) shows encouraging and clinically meaningful anticancer activity in patients with KRAS G12C-mutated advanced pancreatic cancer in…

DetailsCategory: Small MoleculesPublished on Tuesday, 15 February 2022 11:02Hits: 34

Centrally Confirmed Objective Response Rate of 21% and Disease Control Rate of 84%

Largest Dataset and Only Global Clinical Trial to Date to Evaluate the Efficacy and Safety of a KRAS G12C Inhibitor in Advanced Pancreatic Cancer

THOUSAND OAKS, CA, USA I February 14, 2022 I Amgen (NASDAQ: AMGN) today announced the presentation of efficacy and safety data from the CodeBreaK 100 Phase 1/2 trial in patients with KRAS G12C-mutated advanced pancreatic cancer who received LUMAKRAS (sotorasib)*. The data will be presented at the monthly American Society of Clinical Oncology (ASCO) Plenary Series on Feb. 15, 2022. Data show encouraging and clinically meaningful anticancer activity and a positive benefit:risk profile.

"Based on these exciting data, we are expanding CodeBreaK 100 to enroll more patients with pancreatic and other tumor types to better understand the efficacy and safety of LUMAKRAS in tumors outside of non-small cell lung and colorectal cancers," said David M. Reese, M.D., executive vice president of Research and Development atAmgen. "CodeBreaK is the largest and broadest global clinical trial program to date with one of the most robust, centrally reviewed datasets. As we learn more from the extensive data that we collect, we'll continue to invest in the program by expanding cohorts and exploring new combinations so that we can help as many patients as possible."

LUMAKRAS demonstrated a centrally confirmed objective response rate (ORR) of 21% and disease control rate (DCR) of 84% across 38 heavily pre-treated advanced pancreatic cancer patients. Nearly 80% of patients received LUMAKRAS as a third-line or later therapy. Eight of the 38 patients achieved a confirmed partial response (PR) performed by a blinded independent central review (BICR). Two of the eight patients with PR have ongoing responses. Median duration of response was 5.7 months with a median follow-up of 16.8 months as of the data cutoff date of Nov. 1, 2021. The results also show a median progression free survival (PFS) of 4 months and a median overall survival (OS) of almost 7 months. No new safety signals were identified with this study of patients with advanced pancreatic cancers. Treatment-related adverse events (TRAEs) of any grade occurred in 16 (42%) patients with diarrhea (5%) and fatigue (5%) as the most common grade 3 TRAEs. No TRAEs were fatal or resulted in treatment discontinuation.

"After decades of research, current treatments for patients with pancreatic cancer provide limited survival benefit, illustrating the critical need for novel, safe and effective treatment options," said John Strickler, M.D. associate professor of medicine, Duke University School of Medicine and gastrointestinal oncologist. "In the largest dataset evaluating the efficacy and safety of a KRASG12C inhibitor in heavily pretreated advanced pancreatic cancer, sotorasib achieved a centrally confirmed response rate of 21% and a disease control rate of 84%. This is clinically meaningful for patients because there is not an established standard therapy for these patients once they get to a third-line of treatment."

Cancer of the pancreas is a highly lethal malignancy. Itis the fourth leading cause of cancer-related deaths in both men and women in the U.S. with a 5-year survival rate of approximately 10%.1 There is a high unmet need for patients with advanced pancreatic cancer that has progressed after first-line treatment, where FDA-approved second-line therapy has provided survival of about six months and a response rate of 16%.2 After progression on first- and second-line chemotherapy, there are no therapies with a demonstrated survival benefit.2,3 Despite advances in treatment, few improvements have been made to improve diagnosis and treatment of pancreatic cancer.

It is estimated that approximately 90% of patients with pancreatic cancer harbor a KRAS mutation with KRAS G12C accounting for approximately 1-2% of these mutations.4-5

ASCO Plenary Series SessionASCO will host a livestream event on Tuesday, Feb. 15 at 3 p.m. ET featuring presentation of the abstract "First data for sotorasib in patients with pancreatic cancer withKRASp.G12C mutation: A phase I/II study evaluating efficacy and safety"by Dr. John Strickler from Duke University. To participate in the free and open session, participants may register and login at https://www.asco.org/meetings-education/monthly-plenary-series/program.

*LUMAKRAS is marketed as LUMYKRAS (sotorasib) in the European Union and the United Kingdom.

About LUMAKRAS/LUMYKRAS(sotorasib)Amgentook on one of the toughest challenges of the last 40 years in cancer research by developing LUMAKRAS/LUMYKRAS, a KRASG12Cinhibitor.6 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 theKRASG12Cmutation with a once daily oral formulation.7

Amgenis progressing the largest and broadest global KRASG12Cinhibitor 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 KRASG12C inhibitor to receive regulatory approval anywhere in the world with its approval in the U.S., under accelerated approval. LUMAKRAS/LUMYKRAS is also approved in the United Arab Emirates, the European Union, Japan and Switzerland, and in 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 Australia, Brazil, Singapore and Israel. Additionally,Amgenhas submitted MAAs in South Korea, Turkey, Taiwan, Colombia, Thailand, Mexico, Hong Kong, Saudi Arabia, Argentina, Kuwait and Qatar.

LUMAKRAS/LUMYKRAS is also being studied in multiple other solid tumors.8

About CodeBreaKThe CodeBreaK clinical development program forAmgen's drug sotorasib is designed to treat patients with an advanced solid tumor with theKRASG12Cmutation 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 withKRASG12C-mutant solid tumors.7.8Eligible 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.7 The Phase 2 trial in colorectal cancer (CRC) is fully enrolled and results have been published.9

CodeBreaK 200, the global Phase 3 randomized active-controlled study comparing sotorasib to docetaxel in KRASG12C-mutated NSCLC completed enrollment of 345 patients. Eligible patients had previously treated (previous treatment with both platinum doublet chemotherapy and a checkpoint inhibitor), locally-advanced and unresectable or metastatic KRASG12C-mutated NSCLC.The primary endpoint is progression-free survival and key secondary endpoints include overall survival, objective response rate, and patient-reported outcomes.

Amgenalso has several Phase 1b studies investigating sotorasib monotherapy and sotorasib combination therapy across various advanced solid tumors (CodeBreaK 101) open for enrollment. A Phase 2 randomized study will evaluate sotorasib in patients with stage IVKRASG12C-mutated NSCLC in need of first-line treatment (CodeBreaK 201).For information, please visitwww.hcp.codebreaktrials.com.

LUMAKRAS(sotorasib)U.S.IndicationLUMAKRASis indicated for the treatment of adult patients withKRASG12C-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 LUMAKRASfullPrescribing Information.

AboutAmgenOncologyAtAmgenOncology, 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,Amgencontinues to advance the largest pipeline in the Company's history, moving with great speed to advance those innovations for the patientswhoneed them.

AtAmgen, we're advancing oncology at the speed of life.

For more information, follow us onwww.twitter.com/amgenoncology.

AboutAmgenAmgenis 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.

Amgenfocuses 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,Amgenhas 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.

Amgenis one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2021,Amgenwas named one of the 25 World's Best Workplaces by Fortune andGreat Placeto Work and one of the 100 most sustainable companies in the world byBarron's.

For more information, visitwww.amgen.comand follow us onwww.twitter.com/amgen.

1Siegel RL, et al. CA Cancer J Clin. 2022;72:7-33.2Tempero MA, et al. J Natl Compr Canc Netw. 2021;19:439-457.3Wang-Gillam A, et al. Eur J Cancer. 2019;108:78-87.4Nassar AH, et al. N Engl J Med. 2021;384:185-1875Cox AD, et al. Nat Rev Drug Discov. 2014;13:828-851.6Canon J, et al.Nature. 2019;575:217223.7Skoulidis F, et al.N Engl J Med.2021;384:2371-2381.8Hong DS, et al.N Engl J Med. 2020;383:1207-1217.9Fakih MG, et al, Lancet Oncol. 2022.

SOURCE: Amgen

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Lumakras (sotorasib) shows encouraging and clinically meaningful anticancer activity in patients with KRAS G12C-mutated advanced pancreatic cancer in...