AN EARLY-PHASE CLINICAL TRIAL presented April 19 at the American Association for Cancer Research (AACR) Annual Meeting 2026 in San Diego, suggests an experimental KRAS inhibitor can control advanced non-small cell lung cancer that has progressed on other treatments, including other KRAS inhibitors.

The study explored the use of elisrasib, a drug that targets the KRAS G12C mutation, which is the most common alteration in the KRAS gene among people with non-small cell lung cancer. Currently, there are two drugs, Krazati (adagrasib) and Lumakras (sotorasib), that target the KRAS G12C mutation, but cancers carrying this mutation may not respond to these targeted therapies. In addition, half of patients who do have a treatment response will experience progression within six months.

Elisrasib appears to more quickly and strongly engage cells with the KRAS G12C mutation, Byoung Chul Cho, a medical oncologist at Yonsei Cancer Center in Seoul, South Korea, and the study’s presenter, said during a press conference at the AACR Annual Meeting. (The AACR publishes Cancer Today.)

“These new treatments may address challenges, such as brain metastases and resistance to earlier drugs, potentially improving outcomes and redefining care for lung cancer patients with KRAS G12C mutations,” Cho said.

Cho shared data from 99 participants who received a 600-milligram dose of elisrasib. Of these people, 68 had not received a previous KRAS inhibitor, while 31 were treated with prior KRAS inhibitors. Among the 68 people who had not previously received a KRAS inhibitor, 58.8% had their lung cancer shrink after treatment with elisrasib—with one complete response. The median duration of response in this group was 16.5 months. In addition, 98.5% of these people experienced disease control, meaning their cancer shrank or stopped growing. Among the 31 people in the study who previously received a KRAS inhibitor, 32.3% had a response—with a median duration of 15.6 months—and 83.9% experienced disease control.

Researchers took blood samples from most participants prior to treatment to look for traces of circulating tumor DNA, or ctDNA, to measure treatment response. They noted a molecular response—measured as a 90% reduction in the fraction of KRAS mutations in the ctDNA test—in 93% of the patients who had not received an earlier KRAS inhibitor and 80% of those who previously took a KRAS inhibitor.

“That does translate into what looks like high response rates and I think particularly impressive response rates in patients who are resistant or refractory to prior G12C inhibitors,” said Jayesh Desai, a medical oncologist at Peter MacCallum Cancer Centre in Melbourne, Australia, who moderated the discussion at the press conference.

Researchers also noted tumor response in patients with brain metastases, which can be difficult to treat, Cho said.

In the study, 11.5% of people experienced severe side effects that needed medical attention, but most side effects were mild, Cho said. Common side effects included nausea, diarrhea and vomiting.

The phase I/II clinical trial was small and focused on the drug’s safety, dosage and early signs of efficacy. Larger, randomized trials will be needed to confirm the drug’s efficacy and if the responses are sustained, Cho said. Studies are currently exploring both elisrasib on its own and in combination with immune checkpoint inhibitors as a first-line treatment for non-small cell lung cancer.

Eric Fitzsimmons is an editor at Cancer Today.