- Among the more than 2,600 clinical trials testing the most successful type of cancer immunotherapy, only 89, or about 3%, target pancreatic cancer, according to a new analysis unveiled Sunday by the nonprofit Cancer Research Institute.
- Pancreatic cancer remains one of the toughest tumor types to treat, and currently ranks as the third leading cause of cancer-related death in the U.S. — making the relative dearth of immunotherapy trials studying new treatment approaches notable.
- Still, some progress is being made. A study led by the Parker Institute for Cancer Immunotherapy and funded by CRI, results of which were also disclosed Sunday, showed combining immunotherapy together with chemotherapy could hold potential in treating metastatic pancreatic ductal adenocarcinoma, the most common subtype of the cancer.
Since the success of checkpoint inhibitors like Merck & Co.'s Keytruda (pembrolizumab), thousands of clinical trials have begun testing similar drugs or combinations that involve one of the six PD-1 or PD-L1 inhibitors already approved in the U.S.
Much of that research, however, is directed at the same cancer types. While only 89 studies involving a PD-1 or PD-L1 blocker target pancreatic cancer, 535 — or about 20% of the overall study total — are directed against lung cancer.
There are reasons for that disparity, of course. Pancreatic cancer is not considered particularly immunogenic, or likely to spur an immune response — a trait that makes directing immunotherapy against the tumor type difficult. Lung cancer, kidney cancer and melanoma, by contrast, are highly immunogenic.
The cellular environment surrounding pancreatic tumors also might be more inhibitory of immune response, making so-called "immune escape" more likely. And most pancreatic tumors are driven by mutations in a gene known as RAS, which has proved challenging to attack using targeted therapies.
Not surprisingly, then, nearly all of the 89 studies identified by CRI are testing combinations of drugs in hopes of hitting on a more effective treatment.
That's also the approach of the Parker study, which tested either a three- or four-drug combination pairing standard-of-care chemotherapy with one or two immunotherapies.
Two of the four study cohorts received gemcitabine plus Abraxane (nab-paclitaxel) with an experimental immunotherapy that inhibits a protein called CD40. The other two added Bristol-Myers Squibb's Opdivo (niovlumab) on top of that triplet.
Results presented Sunday at the annual meeting of the American Association for Cancer Research showed treatment helped to shrink tumors in 58% of the 24 evaluable patients. All of those responses were partial, while eight study participants experienced stable disease.
Additionally, analysis of circulating tumor DNA in the blood found a "marked and rapid decrease" in mutant KRAS DNA associated with therapy in some patients.
Several patients remained on treatment for roughly a year, although most experienced serious side effects. Four patients died, two from disease progression and two from septic shock associated with neutropenia.
"Compared with most other cancers, pancreatic cancer has a challenging prognosis, so to see patients continuing on the same treatment for a year and beyond is very promising," said Eileen O'Reilly, co-lead author of the study and associate director for clinical research at a pancreatic cancer center at Memorial Sloan Kettering, in a statement.
Bristol-Myers and Apexigen, which is developing the the anti-CD40 antibody used in the study, collaborated with the Parker Institute and CRI. The trial is the first to emerge from a clinical research partnership inked between Bristol-Myers, the Parker Institute and CRI in March 2017.
Based on the initial study results, the partners have advanced testing of the combination into Phase 2.