Amgen to Initiate Phase 3 Study of Sotorasib for NSCLC, Based on Results From CodeBreaK 101 Trial

Amgen has initiated a phase 3 study of sotorasib (Lumakras) plus carboplatin and pemetrexed in the first-line treatment of KRAS^G12C-mutant advanced non–small cell lung cancer (NSCLC) due to results from the CodeBreaK 101 clinical trial (NCT04185883). The results of the study were included as an oral presentation at the International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer.¹

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The expected enrollment of the CodeBreaK 202 study (NCT05920356) is expected to start before the end of 2023.¹

"We are delighted to see the positive data from the global CodeBreaK 101 trial further validate our approach to move [sotorasib] earlier within the treatment paradigm through novel therapeutic combinations," David M. Reese, MD, executive vice president of Research and Development at Amgen, said in a statement. "Notably, these results follow and further expand upon the phase 2 investigator-led data demonstrating favorable efficacy and safety of [sotorasib] plus carboplatin and pemetrexed in the first-line treatment of patients with KRASG12C-mutated NSCLC."¹

The findings confirmed that individuals treated with the combination in the first-line setting achieved a confirmed objective response rate (ORR) of 65%, with a 100% disease control rate (DCR).¹ Additionally, the results of the study showed that in the second line, the ORR was 54% with a DCR of 85%. For patients with protein ligand-1 expressions less than 1%, the ORR was 62% in the first line and 50% in the second line.¹

Investigators reported preliminary rapid and durable responses with a 3-month follow up. At this time, the progression-free survival and overall survival data were immature.¹

"Combination treatment is an important approach to prevent or delay the onset of drug resistance and improve the depth and durability of targeted response in KRAS^G12C­­-mutated NSCLC," Jeffrey M. Clarke, MD, oncologist and associate professor of medicine at the Duke Cancer Institute at Duke University, said in the statement. "The CodeBreaK 101 results show exciting efficacy with sotorasib plus chemotherapy and, importantly for a combination treatment, a safety profile consistent with the individual therapies. These data warrant continued investigation in larger trials."¹

According to the investigators, the combination therapy had treatment-related adverse events (AEs) that were consistent with sotorasib and the platinum doublet-based approaches. The most common AEs included neutropenia/neutrophil count decrease at 53%, anemia at 39%, and thrombocytopenia/platelet count decrease at 37%. Additionally, there were not fatal AEs in the study.¹

Previously, Amgen announced results from the CodeBreaK clinical trial program that further emphasized the efficacy of sotorasib with KRAS^G12C-mutated NSCLC and metastatic colorectal cancer. These results were presented at the American Society of Clinical Oncology Annual (ASCO) Meeting 2023.²

The results were supported by data from the SCARLET trial, which were also presented at ASCO. The findings indicated that it was safe and effective to use sotorasib in combination with platinum-based chemotherapy as first-line treatment of individuals with advanced NSCLC and a KRAS^G12C mutation.²

In the CodeBreaK 200 trial (NCT04303780), the investigators found that sotorasib demonstrated delayed time to progression and longer central nervous system progression-free survival compared to docetaxel.²

Reference

1. Amgen presents new Lumakras (sotorasib) plus chemotherapy data in first-line KRAS G12C NSCLC at WCLC. News release. Amgen. September 10, 2023. Accessed September 11, 2023. https://wwwext.amgen.com/newsroom/press-releases/2023/09/amgen-presents-new-lumakras-sotorasib-plus-chemotherapy-data-in-firstline-kras-g12c-nsclc-at-wclc
2. Gallagher A. New data from CodeBreaK clinical trial demonstrate efficacy of sotorasib for NSCLC, colorectal cancer. Pharmacy Times. June 12, 2023. Accessed September 11, 2023. https://www.pharmacytimes.com/view/new-data-from-codebreak-clinical-trial-demonstrate-efficacy-of-sotorasis-for-nsclc-colorectal-cancer