A drug recently approved to treat pancreatic cancer has also shown early promise in lung cancer according to the results of a new trial.

The work published in The New England Journal of Medicine tested daraxonrasib, a new targeted drug, on 136 patients with non-small cell lung cancer (NSCLC) whose cancer had spread to other parts of the body. The patients had all received previous other treatments like chemotherapy and all of them had DNA mutations affecting a protein called RAS, which is a molecular switch which can get stuck “on,” driving growth of cancer cells. Daraxonrasib blocks this switch and inhibits cancer cell growth.

“In lung cancer we find KRAS mutations in not every patient, but in about 30% of patients," said Kathryn Arbour, MD, medical oncologist at Memorial Sloan Kettering Cancer Center in New York City and leader of the clinical trial. “Given the overall incidence of lung cancer and how many cases are diagnosed in the United States each year, this is still a large number of patients.”

The study showed that 31-37% of patients with NSCLC responded to the drug, depending on the dose they were given. This may initially not seem like a lot and daraxonrasib wasn’t directly compared to standard treatment options within the trial, but the early results indicate a potential improvement compared to chemotherapy.

“Typically, the chemotherapies that we would otherwise use in this setting may work and lead to substantial shrinkage in only maybe 10% of cases. The fact that more than a third of patients are really seeing shrinkage of their tumor is actually quite impressive,” said Dr Arbour, also noting that there are early indications that the responses can last for a long time, which is not typically seen with chemotherapy in these patients.

Targeting RAS in NSCLC is not entirely new. Two drugs are already approved for use, but crucially they only work on patients who have a very specific DNA mutation in the KRAS gene, G12C. Daraxonrasib is designed to work for patients with a much broader range of RAS mutations in their tumors.

“What’s distinctly different about Daraxonrasib is it is a multi‑RAS inhibitor. It can inhibit many different types of KRAS mutations, so it can broaden the reach of who can receive a targeted therapy in patients with lung cancer that have these mutations,” said Dr Arbour.

One of the primary goals of the trial was to see if the drug was safe to use in this patient population. Almost all patients in the trial had at least mild side effects, with half having moderate or more severe side effects.

“In small trials like this, when toxicities are reported, sometimes it can be difficult to tease out what is related to their overall cancer course or other medical issues. The side effects that we’ve seen with this drug that we think are truly related to the drug itself are fairly similar to what has been reported with pancreas cancer, and that is most commonly a rash, and also nausea, vomiting, diarrhea, and sometimes some irritation of the mouth called mucositis," said Dr Arbour.

Although the early results are promising, the trial only tested the drug on a small number of patients with very advanced disease. More evaluation is needed to see wehther it can gain FDA-approval for use in people with advanced NSCLC with RAS mutations.

“There is a phase III clinical trial that’s ongoing in patients with lung cancer who’ve been previously treated with both chemotherapy and immunotherapy, our standard first‑line treatments. Ultimately, if successful, that trial will lead to what we hope will be FDA approval of the medicine within lung cancer patients,” said Dr Arbour.

The results also raise the possibility that multi-RAS inhibitors like Daraxonrasib could eventually be used to treat other cancers driven by RAS mutations, potentially expanding targeted treatment to patients who currently have few options.