photo of KRAS inhibitors researcher Miriam Molina Arcas, PhD

The research may eventually help clinicians optimize therapy with KRAS inhibitor immune checkpoint inhibition.

New research suggests that some patients with lung cancer might benefit from combining a KRAS inhibitor with immune checkpoint inhibition, according to a new report.

The study, published in Science Advances, is based on experiments in mice, but the authors say the findings could help direct future clinical trials in humans. They noted that a significant unmet need remains in lung cancer treatment.

Despite recent advances in immunotherapy, lung cancer remains the deadliest cancer type, killing 1.8 million people each year. The most common type of lung cancer, non–small cell lung cancer (NSCLC), has a 5-year survival rate of just 25%, the authors noted.

The introduction of immune checkpoint blockades, such as anti–programmed cell death protein-1 (PD-1) therapy, has led to prolonged responses in some patients.

“However, only a minority of patients respond and, of those that do, many develop resistance over time,” the authors wrote.

Thus, a significant amount of current research focuses on trying to find ways to combine immune checkpoint blockades with other therapies in order to boost efficacy.

One potential strategy for a combination therapy is KRAS inhibition. KRAS is a gene that helps control cell growth and death. KRAS mutations are present in about one-third of lung adenocarcinoma cases, making it a promising therapeutic target, the study authors said. Historically, they noted, inhibiting KRAS was “notoriously difficult.” However, last year, the FDA granted an accelerated approval to sotorasib (Lumakras) for patients with KRAS G12C–mutated NSCLC. The G12C mutation is present in about 40% of patients with KRAS-mutated NSCLC.

The investigators therefore decided to see whether combining KRAS inhibition with immune checkpoint blockade would lead to positive effects in mice. They found that it did—but only for certain patients.