Amgen has unveiled exciting findings from a segment of the CodeBreaK 101 clinical trial, a Phase 1b study investigating the potential of Lumakras (sotorasib) in combination with carboplatin and pemetrexed for adult patients grappling with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC). These remarkable results took center stage in an oral presentation at the 2023 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer (IASLC) in Singapore on Sunday, September 10.
“We are delighted to see the positive data from the global CodeBreaK 101 trial further validate our approach to move LUMAKRAS earlier within the treatment paradigm through novel therapeutic combinations. Notably, these results follow and further expand upon the Phase 2 investigator-led data demonstrating favorable efficacy and safety of LUMAKRAS plus carboplatin and pemetrexed in the first-line treatment of patients with KRAS G12C-mutated NSCLC.”
– David M. Reese, M.D., executive vice president of Research and Development at Amgen
For patients in the first-line treatment category (n=20), the confirmed objective response rate (ORR) soared to an impressive 65%, accompanied by an astounding 100% disease control rate (DCR) (95% CI: 83.2, 100). In the second-line treatment group (n=13), the ORR stood at 54%, paired with a robust DCR of 85% (95% CI: 54.6, 98.1). Even among patients with low protein ligand-1 (PD-L1) expression, the results were striking, with a 62% ORR in the first-line setting and a 50% ORR in the second-line setting. Importantly, these responses were characterized by their rapid onset and long-lasting impact. However, it’s essential to note that data on progression-free survival (PFS) and overall survival (OS) are still evolving.
Related: Advancing Precision Oncology: Targeting KRAS Mutations With LUMAKRAS And KRAZATI
The combination of Lumakras and chemotherapy yielded treatment-related adverse events (TRAEs) that align with expectations based on Lumakras and other platinum doublet-based therapies. The most prevalent TRAEs included neutropenia/neutrophil count decrease (53%), anemia (39%), and thrombocytopenia/platelet count decrease (37%). Encouragingly, no fatal adverse events were recorded.
“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 G12CĀĀ-mutated NSCLC. 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.”
– Jeffrey M. Clarke, M.D., oncologist and associate professor of medicine, Duke Cancer Institute at Duke University
In light of these groundbreaking findings, Amgen is forging ahead with a Phase 3 study evaluating Lumakras alongside carboplatin and pemetrexed in first-line treatment for KRAS G12C-mutant advanced NSCLC, irrespective of programmed cell death PD-L1 status (CodeBreaK 202; NCT05920356). Enrollments for this pivotal study are set to commence by the close of 2023.
Related: Sotorasib Vs Docetaxel In KRAS G12C-Mutated NSCLC: ASCO 2023 Highlights
This development marks a significant stride in the quest for innovative treatments and renewed hope for patients battling KRAS G12C-mutated advanced NSCLC, showcasing the potential for Lumakras to redefine the landscape of lung cancer therapy. Stay tuned for further updates as this promising journey unfolds.
