Clinical Data From Full Phase 1 Cohort Of Investigational Sotorasib Published In New England Journal Of Medicine

THOUSAND OAKS, Calif., Sept. 20, 2020 /PRNewswire/ — Amgen (NASDAQ: AMGN) today announced that updated data from the full Phase 1 cohort of the CodeBreaK 100 clinical study, evaluating sotorasib (proposed INN for AMG 510) in 129 patients across multiple advanced solid tumors, were published in the New England Journal of Medicine (NEJM). Data from 59 patients with advanced non-small cell lung cancer reported in the NEJM manuscript were also featured today during an oral presentation at ESMO 2020.

“CodeBreaK 100 is the largest Phase 1/2, and first-in-human, clinical study for a KRASG12C inhibitor,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “Earlier this year at ASCO, we reported encouraging early data in patients with advanced colorectal cancer and a number of other solid tumors. We’re pleased to share these updated Phase 1 results, particularly in patients with advanced non-small cell lung cancer, and look forward to the Phase 2 readout in this heavily pretreated population later this year.”

Sotorasib demonstrated confirmed objective response rate (ORR) and disease control rates (DCR) of 35.3% and 91.2%, respectively, in 34 heavily pretreated patients (median of two prior lines of therapy) with NSCLC, who were treated with the 960 mg daily dose (data cutoff of June 1, 2020).

Anticancer activity was seen across all dose levels in patients with NSCLC, with a confirmed ORR of 32.2% and DCR of 88.1%, and median duration of response of 10.9 months, with 10 of 19 responders still in response as of the data cutoff. Tumor shrinkage was observed in 71.2% of patients at the first week-6 assessment. Median progression-free survival (mPFS) in patients treated with sotorasib was 6.3 months.

Safety and tolerability in patients with NSCLC were consistent with previously seen CodeBreaK 100 results. No dose-limiting toxicities were observed and there were no fatal treatment-related adverse events (TRAEs). The most common TRAEs were diarrhea (25.4%), alanine aminotransferase (ALT) increase (20.3%), aspartate aminotransferase (AST) increase (20.3%), fatigue (10.2%) and nausea (10.2%). Eleven (18.6%) patients had grade 3 or higher TRAEs, one of whom had grade 3 TRAEs of ALT and AST increases that led to discontinuation of treatment.

“These latest results show that sotorasib continues to demonstrate encouraging clinical benefit in heavily pretreated patients with KRAS G12C-mutant tumors,” said lead author David S. Hong, M.D., Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, TX. “The results also establish a compelling trend in tumor shrinkage and median progression-free survival with a positive benefit-risk profile.”

The ESMO oral presentation included Phase 1 NSCLC results published in NEJM, as well as data on potential biomarkers of response to sotorasib that demonstrated clinical activity across a range of KRAS G12C mutant allele frequencies (MAFs), PD-L1 tissues expression levels, tumor mutational burden (TMB) plasma levels and tissue co-mutational profiles.

“KRAS G12C is a driver of multiple solid tumor types and is particularly prevalent in non-small cell lung cancer,” said Fabrice Barlesi, M.D., Ph.D., Professor of Medicine at Aix-Marseille University, Medical Director of Gustave Roussy Institute, Paris, France. “Despite this, there are currently no approved targeted therapy options for KRAS G12C and patients remain in need of additional treatment options, which makes these new findings particularly important.”

About KRAS

The RAS gene family, which has been the subject of almost four decades of research, contains some of the most frequently mutated oncogenes in human cancers.^1,2 Targeting the KRAS protein, the most commonly altered family member in solid tumors, has been one of the toughest challenges in cancer research.¹ A specific mutation known as KRAS G12C, is a major driver of tumor growth, occurring broadly across solid tumor indications. In the U.S., about 13% of patients with non-small cell lung cancer harbor the KRAS G12C mutation.^3,4 It is also found in approximately 3-5% of colorectal cancers and 1-2% of numerous other solid tumors, making this among the most broadly represented mutations across cancer patient subgroups.^5,6,7,8,9. With the discovery of a unique surface groove in the KRASG12C protein, Amgen developed and advanced the first investigational KRASG12C inhibitor into the clinic and is exploring the potential of KRASG12C inhibition across multiple tumor types for patients who remain in dire need of treatment options.^1,10

About CodeBreaK

The CodeBreaK clinical trial program for Amgen’s investigational 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.

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 1 study is safety, and key secondary endpoints include objective response rate (assessed every six weeks), duration of response and progression-free survival. Patients were enrolled in four dose cohorts: 180 mg, 360 mg, 720 mg and 960 mg, taken orally once a day.

Amgen’s single-arm Phase 2 trials in both non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) (also part of CodeBreaK 100) are now fully enrolled. The potentially registrational Phase 2 trial in NSCLC is on track for data readout later in 2020 and a global Phase 3 randomized active-controlled confirmatory study comparing sotorasib to docetaxel in NSCLC (CodeBreaK 200) has begun recruiting. The Phase 2 CRC trial is expected to have a data readout in 2021. Amgen is also currently enrolling six Phase 1b combination studies across various advanced solid tumors (CodeBreaK 101).

Additional information about CodeBreaK clinical trials can be found at http://www.codebreaktrials.com.

About Amgen Oncology

Amgen Oncology is searching for and finding answers to incredibly complex questions that will advance care and improve lives for cancer patients and their families. Our research drives us to understand the disease in the context of the patient’s life – not just their cancer journey – so they can take control of their lives.

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.

At Amgen, we are driven by our commitment to transform the lives of cancer patients and keep them at the center of everything we do. 

To learn more about Amgen’s innovative pipeline with diverse modalities and genetically validated targets, please visit AmgenOncology.com. 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.

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

Forward-Looking Statements
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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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References

SOURCE Amgen
 
 

Posted: September 2020

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