New pancreatic cancer drug

 

A transformative new drug for pancreatic cancer. Pancreatic adenocarcinoma is one of the deadliest cancers, with a five-year survival rate of just 13 percent; advances in therapy against the disease have been slow. A key reason is that around three-quarters of these cancers are driven by mutations in KRAS, a protein that has been considered essentially undruggable because it lacks an obvious binding site for a drug molecule. A new treatment, called daraxonrasib, gets around this by first binding to another protein in the cell, cyclophilin A, forming a complex that can then latch onto and blockmutant KRAS, cutting off the signal that drives tumor growth. 

In a phase three trial of around 500 patients with metastatic pancreatic cancer who had already progressed while on chemotherapy, the company reported a median overall survival of 13.2 months with daraxonrasib versus 6.7 months with chemotherapy, roughly doubling survival. That is an unprecedented result for a cancer that has so far been devastating and stubbornly resistant to progress. These are topline numbers released by the company, and detailed data on safety and subgroup analyses will help understand the result better. The drug also appears to cause significant side effects, including serious bleeding and skin problems. But it may also be one of the biggest cancer breakthroughs of the year, if not decade.

This trial enrolled patients with late-stage pancreatic cancer, but phase three trials are also underway testing the drug as a first-line treatment and as an add-on for patients whose tumors are still surgically treatable. The drug is also being tested in lung cancer, and could be expanded further; KRAS mutations drive roughly 20 percent of all human cancers. Since a viable mechanism for targeting KRAS has been demonstrated to work in patients, researchers can focus on iterating, improving safety, optimizing dosing, testing combinations, pushing the drug earlier in the disease course, and expanding its use for other cancers.

https://www.targetedonc.com/view/daraxonrasib-shows-significant-os-benefit-in-metastatic-pancreatic-cancer


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