Pancreatic cancer is difficult to treat and has one of the lowest survival rates of all malignancies. But novel targeted therapies and a vaccine offer renewed hope.

 

Daraxonrasib is an oral RAS(ON) inhibitor that targets previously “undruggable” RAS mutations. In April, Revolution Medicines announced results from a Phase III trial showing that daraxonrasib alone doubled overall survival time compared with chemotherapy for previously treated patients, from 6.7 to 13.2 months. Phase I/II results showed that daraxonrasib also holds promise for patients starting treatment for the first time. Revolution has a new type of Food and Drug Administration priority voucher that shortens review time to just one to two months; in May, the agency allowed the company to start an expanded access protocol.

 

Another targeted therapy, elraglusib, blocks GSK-3-beta, a protein that plays a role in tumor growth and immune suppression. In a Phase II trial of previously untreated patients with metastatic pancreatic cancer, elraglusib plus chemotherapy extended survival by only 2.9 months compared with chemotherapy alone, but those randomized to the combination were twice as likely to be alive at one year (44% versus 22%).

 

Finally, a customized mRNA vaccine appears to lower the risk of pancreatic cancer progression for at least six years. An ongoing Phase I trial is testing autogene cevumeran, a personalized vaccine made from a patient’s tumor after surgery. Eight of 16 patients with operable pancreatic cancer who received the vaccine plus an immune checkpoint inhibitor and chemotherapy had strong, durable T-cell responses.

 

At the 2024 American Association for Cancer Research Annual Meeting, Vinod Balachandran, MD, of Memorial Sloan Kettering Cancer Center, reported that six of the eight responders remained cancer-free over three years of follow-up, while most of the non­responders relapsed. At this year’s meeting, he reported that seven of the eight responders were still alive up to six years after surgery, while all but two of the nonresponders had died.