On January 28, 2021 Amgen (NASDAQ: AMGN) reported results from the Phase 2 cohort of the CodeBreaK 100 clinical study evaluating investigational sotorasib (AMG 510) in 126 patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) (Press release, Amgen, JAN 28, 2021, View Source [SID1234574396]). The results will be presented during the Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer (WCLC) and are the first from a completed pivotal Phase 2 study in NSCLC with a median follow-up of more than one year.

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Sotorasib demonstrated a confirmed objective response rate (ORR) and disease control rate (DCR) of 37.1% and 80.6%, respectively, and a median duration of response of 10 months (data cutoff of Dec.1, 2020; median follow-up time was 12.2 months). The results also highlighted that sotorasib is the first KRASG12C inhibitor to show progression-free survival (median of 6.8 months) in a Phase 2 study, which is consistent with earlier Phase 1 results in previously treated patients with KRAS G12C-mutated advanced NSCLC.

Patients were treated with sotorasib 960 mg once daily orally. Prior to the trial, 81% of patients had progressed on both platinum-based chemotherapy and PD1/L1 inhibitors, with the remainder progressing after having received one of these therapies.

"Patients with advanced non-small cell lung cancer who have failed first-line treatment face extremely poor outcomes with limited treatment options available to them, and Amgen has been committed to changing that," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "Targeting KRAS has been a 40-year quest by scientists and researchers around the world, and we are extremely pleased that sotorasib has successfully demonstrated rapid, deep and durable responses in this registrational Phase 2 study that was conducted in record time. We are proud that sotorasib may potentially become the first approved targeted therapy for these patients."

Over 80% of patients achieved disease control, including three complete responses and 43 partial responses, and the median best tumor shrinkage among all responders (n=46) was 60%. The median time to objective response was 1.4 months. Sotorasib had a favorable benefit-risk profile with most treatment-related adverse events (TRAEs) mild-to-moderate (grade 1 or 2) and no treatment-related deaths. Grade 3 TRAEs were reported in 25 (19.8%) patients and only one patient (0.8%) reported a Grade 4 TRAE. The most frequently reported TRAEs (any grade) were diarrhea (31.0%), nausea (19.0%), increased alanine aminotransferase (15.1%) and increased aspartate aminotransferase (15.1%). TRAEs led to treatment discontinuation in only 7.1% of patients.

"These results are encouraging and clinically meaningful for patients with advanced NSCLC harboring the KRAS G12C mutation," said Bob T. Li, MD, PhD, MPH, medical oncologist and principal investigator at Memorial Sloan Kettering Cancer Center. "These are patients who have progressive disease after standard treatment, so they need additional treatments, and the fact that we are seeing rapid tumor shrinkages and durable responses in these patients, is for me a step forward and a win for patients."

In exploratory analyses, encouraging tumor response to sotorasib was observed across a range of biomarker subgroups, including patients with negative or low PD-L1 expression level and those with STK11 mutation. This co-mutation has been associated with poor outcomes in NSCLC patients treated with checkpoint inhibitors and chemotherapy.

"Despite recent treatment advances, survival outcomes remain poor for patients with advanced stage non-small cell lung cancer on second and third-line therapies with the KRAS G12C mutation. Currently there are no targeted treatment options for them, and I am excited about the advances that Amgen is pioneering in this field to potentially help improve patient outcomes," said Dr. Upal Basu Roy, vice president of Research, LUNGevity.

Following recent regulatory submissions in the U.S., European Union, Australia, Brazil, Canada and UK, Amgen is working with regulatory agencies across the globe to bring sotorasib to NSCLC patients as quickly as possible. Sotorasib has achieved Breakthrough Therapy Designation in the U.S.

NSCLC accounts for 80%-85% of all lung cancers, and most patients (66%) have advanced or metastatic disease at initial diagnosis.1,2 KRAS G12C is one of the most common driver mutations in NSCLC and there is a high unmet need and poor outcomes associated in the second-line treatment of KRAS G12C driven NSCLC.3 In the U.S., about 13% of patients with NSCLC harbor the KRAS G12C mutation,4,5 and each year approximately 25,000 new patients in the U.S. are diagnosed with KRAS G12C-mutated NSCLC.6

Amgen Webcast Investor Call
Amgen will host a webcast call for the investment community in conjunction with WCLC 2020. On Friday, Jan. 29, 2021, at 5 p.m. PST, David M. Reese, M.D., executive vice president of Research and Development at Amgen, along with members of Amgen’s clinical development team and clinical investigators, will discuss registrational Phase 2 NSCLC data being presented on the Company’s investigational KRASG12C inhibitor sotorasib.

Live audio of the conference call will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public. The webcast, as with other selected presentations regarding developments in Amgen’s business given at certain investor and medical conferences, can be accessed on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

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

About Sotorasib
Amgen has taken on one of the toughest challenges of the last 40 years in cancer research by developing sotorasib, an investigational KRASG12C inhibitor.7 Sotorasib was the first KRASG12C inhibitor to enter the clinic and is being studied in the broadest clinical program exploring 10 combinations with global sites spanning five continents. In just over two years, the sotorasib clinical program has established the largest clinical data set with more than 700 patients studied across 13 tumor types to date.

Sotorasib has demonstrated a positive benefit-risk profile with fast, deep and durable anticancer activity in patients with NSCLC harboring the KRAS G12C mutation with a once daily oral formulation. Promising responses have also been observed in multiple other solid tumors.8

About CodeBreaK
The CodeBreaK clinical development 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 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. The Phase 2 trial in colorectal cancer (CRC) is fully enrolled and topline results are expected in 2021.

A global Phase 3 randomized active-controlled study comparing sotorasib to docetaxel in patients with KRAS G12C-mutated NSCLC (CodeBreaK 200) is currently recruiting. Amgen also has more than 10 Phase 1b combination studies across various advanced solid tumors (CodeBreaK 101) open for enrollment.