East Montgomery Times

Researchers from the Perelman School of Medicine at the University of Pennsylvania and Penn Medicine’s Abramson Cancer Center have found that combining immunotherapy with a new type of inhibitor targeting KRAS mutations can extend the effectiveness of pancreatic cancer treatment. The study, published in Cancer Discovery, indicates that this combination could be promising for future clinical trials.

Pancreatic cancer is known for its poor prognosis due to its tendency to spread before diagnosis, leaving limited treatment options. Nearly 90% of these cancers are driven by KRAS mutations, which have been difficult to target effectively. In 2021, a KRAS inhibitor was approved for non-small cell lung cancer with KRAS G12C mutations, but resistance developed quickly in some cases.

"We’ve been excited by the prospect of RAS inhibition for pancreatic cancer," said Ben Stanger, MD, PhD. "This research shows that newer RAS inhibition tools may have an immune stimulatory effect."

The study involved RAS(ON) multi-selective inhibitors like daraxonrasib (RMC-6236) and RMC-7977. These agents differ from other KRAS inhibitors by targeting multiple forms of RAS mutations. "The benefit of this ‘multi-selective’ approach is that the inhibitors are designed to inhibit multiple RAS mutations," explained Robert Vonderheide, MD, DPhil.

In preclinical models using a Penn-developed immunocompetent model for pancreatic ductal adenocarcinoma, combining these inhibitors with immunotherapy led to tumor shrinkage in all cases and complete response in half.

Daraxonrasib is currently being tested in clinical trials across the United States. A trial involving RAS(ON) inhibitors combined with other anticancer agents is open at several sites nationwide.

"We’re hopeful that we’re starting to crack the code on immunotherapy and RAS therapy for pancreatic cancer," Vonderheide said.

The study received support from Revolution Medicines and various organizations including the National Institutes of Health and Department of Defense.

For more information about joining a clinical trial at Penn Medicine's Abramson Cancer Center, visit their Clinical Trial Information Service online or call 1-855-216-0098.