Pancreatic cancer remains one of the hardest cancers to treat. Often diagnosed at an advanced stage, it develops tactics that thwart our best treatments. Fortunately, a new three-headed approach might be able to flank these tricky tumors, according to results from a Cancer Research Institute-funded study just published in The Lancet Oncology.
Despite their benefits in other forms of disease, checkpoint immunotherapies—especially those that target the PD-1/PD-L1 pathway—don’t work well in pancreatic cancer. They’re designed to block immune “brakes” and support T cell responses, but there often aren’t enough T cells within pancreatic tumors to make a difference.
That’s where the second immunotherapy comes in. In contrast to PD-1, the CD40 pathway is an immune “gas pedal.” By pushing it, the doctors hoped to activate the conductors of the immune system, known as dendritic cells, which are capable of orchestrating T cell responses against cancer. Then, the thinking went, PD-1 blockade would act to boost or maintain these responses.
And it appears to have worked, at least in some of the patients treated in the study.
Of the twenty-four patients with metastatic pancreatic cancer who received this combination plus chemotherapy, fourteen saw their tumors shrink, according to phase 1b results from the PRINCE clinical trial, the first study to emerge from a partnership between CRI, the Parker Institute for Cancer Immunotherapy, and Bristol Myers Squibb (BMS). Apexigen, Inc., who provided the CD40-targeting drug APX005M, also collaborated on the trial.
The novel CD40-targeting approach employed in PRINCE was based on rigorous science done by Robert H. Vonderheide, M.D., D.Phil., the director of the University of Pennsylvania’s Abramson Cancer Center. Vonderheide, a member of the CRI Anna-Maria Kellen Clinical Accelerator leadership and a PICI investigator, is also the principal investigator of the PRINCE trial. Long before he translated his discoveries to help human patients, he first recognized the potential value of this pathway more than a decade ago in his efforts to cure cancer in our canine companions.
Now, with the phase 2 portion of the study fully enrolled, Vonderheide and his collaborators are hopeful that they’ll continue to see the benefits of this approach—and ultimately provide a new therapeutic option for people with pancreatic cancer.
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