Early trial shows possibility of knocking down a ‘daunting’ cancer’s defense.
A strategy Dr. Sunil Hingorani helped develop to knock down one of the many defenses that make this cancer so fearsome shows continued potential today as he presented the results of a Phase 2 trial of an experimental drug at the American Society for Clinical Oncology annual meeting. In certain metastatic pancreatic cancer patients, Hingorani reported, adding the drug to a standard chemo regimen lengthened the time patients had before their cancer progressed by an average of four months - a notable increase in this cancer.

The results, Hingorani said, reassure him that it was the right move to advance the drug, called PEGPH20, into the worldwide Phase 3 trial that opened last year.

“We still haven’t fully proven anything yet, strictly speaking,” cautioned Hingorani, who is the Phase 2 trial’s leader and a faculty member at Fred Hutchinson Cancer Research Center. “But I think this strategy is very rational. Let me put it this way: I think it would be irresponsible not to finish the global Phase 3 trial as the most rigorous test of this hypothesis. I think we’re obligated now to answer the question.”

In many pancreatic cancers, the tumors have very high internal pressures that collapse local blood vessels and prevent cancer–killing drugs from getting in. PEGPH20 reduces those pressures so chemotherapies circulating in the blood can penetrate tumors.

In the industry–sponsored, Phase 2 trial, called Halo 202, patients with late–stage pancreatic cancer were randomly assigned to receive a standard of care, first–line combination chemotherapy either with or without PEGPH20. The experimental drug, which was created from the blueprint of a naturally occurring enzyme, breaks down a molecule called hyaluronic acid that is produced in bulk by many pancreatic cancers.

When the results of all 234 evaluable patients on Halo 202 were grouped together, the apparent benefit of PEGPH20 was small ? a matter of just a couple extra weeks of progression-free survival.

But a stark difference emerged when the results were divided up by how much of the drug’s target, HA, patients’ tumors contained: In the subset of 80 patients whose tumors had a lot of HA, adding PEGPH20 to chemo resulted in an average of 9.2 months before disease progression; with chemo alone, this timespan was just 5.2 months.