Amgen announced Tuesday that initial Phase III data of Lumakras (sotorasib) in KRAS G12C-mutated non-small cell lung cancer (NSCLC) met the primary endpoint of progression-free survival.
The early readout points to a significant survival benefit associated with Lumakras treatment compared to intravenous docetaxel chemotherapy, the standard of care.
These findings come from the CodeBreaK 200 trial, a randomized and active-controlled study that enrolled more than 340 patients who had previously been treated with at least a platinum-based doublet chemotherapy and checkpoint inhibitor therapy. All trial participants also had unresectable and metastatic tumors that harbored the G12C mutation in the KRAS gene, the most common genetic alteration in NSCLC.
David M. Reese, M.D., executive vice president of research and development at Amgen, said in a statement that more in-depth data analyses are still ongoing and that the company will reveal more details at an upcoming medical conference.
Lumakras is a highly specific KRAS G12C inhibitor that deactivates the mutant protein by forming an irreversible covalent bond with aberrant cysteine residue. In May last year, Lumakras became the first-ever FDA-approved drug for the treatment of this specific form of NSCLC. Since then, the pharma giant has also initiated a Phase III study of the drug in colorectal cancer, while continuing several studies in lung cancer.
In early August, Amgen released mixed results from two of these trials. The Phase Ib CodeBreaK 100/101 study showed that while combination treatment with pembrolizumab or atezolizumab was effective, inducing an objective response rate of 29%, Lumakras also caused high liver toxicity. Another dose-exploration study under CodeBreaK 101 also showed a good response after Lumakras treatment, accompanied by high rates of side effects.
Lumakras' greenlight was granted under the agency's accelerated approval scheme, which lets the FDA accept a surrogate endpoint as the basis of their regulatory nod but is only applicable for drugs that treat serious diseases for which there are very few treatment options.
The Race Heats Up
Also seeking accelerated approval is California cancer company Mirati Therapeutics, whose NSCLC hopeful adagrasib is awaiting the FDA's verdict. The regulatory body is expected to reach a decision by Dec. 14.
Like Amgen's Lumakras, adagrasib is also a KRAS G12C inhibitor that works by selectively and irreversibly binding to the mutant protein, keeping it inactive. In the Phase II KRYSTAL-I study, Mirati's candidate achieved an objective response rate of 43% and a disease control rate of 80% in nearly 120 NSCLC patients harboring the mutation.
Adagrasib's effects were also durable, lasting for a median of 8.5 months. The average progression-free survival in this trial was 6.5 months. Early data from KRYSTAL-I formed part of adagrasib's new drug application that Mirati filed to the FDA, for which the accelerated approval is pending.
The California biotech presented more promising data for adagrasib at the Annual Meeting of the American Society of Oncology last June.
Drawing from the Phase Ib cohort of KRYSTAL-I, Mirati showed that adagrasib could elicit an intracranial response in about a third of KRAS G12C-mutated NSCLC patients whose tumors had already metastasized to the brain. Three of these responders showed complete treatment responses following adagrasib administration. Mirati's candidate led to an intracranial disease control rate of 84%.
Mirati has also filed a marketing authorization application for adagrasib with the European Medicines Agency.