Combining chemotherapy with an experimental enzyme that lowers pressure within tumors seems to double the amount of time certain patients with metastatic pancreatic cancer have before their disease progresses, suggests an interim analysis of data from an ongoing phase 2 trial. However, the trial must be completed before any definitive conclusions can be drawn, cautioned study principal investigator and pancreatic cancer expert Dr. Sunil Hingorani of Fred Hutchinson Cancer Research Center.
“For me, this ― at an absolute minimum ― says ‘finish this trial,’” said Hingorani, who is presenting the interim results of the Halozyme Therapeutics-sponsored Halo 202 trial this Sunday at the annual meeting of the American Society for Clinical Oncology. The meeting, which begins today in Chicago, runs through June 2.
The trial combines the latest first-line, standard-of-care combination chemotherapy for advanced pancreatic cancer with an enzyme called PEGPH20 that breaks down hyaluronic acid, or HA. HA is a molecule that absorbs water and serves as a natural shock absorber in knee joints. But it’s also produced in high amounts in some tumors and has been linked to a poor prognosis.
In high-HA tumors, the water-loving HA sucks the moisture from surrounding tissues into the tumor, leading to such high pressures that drugs travelling through the bloodstream can’t get in to effectively attack cancer cells.
PEGPH20 is a version of the naturally occurring hyaluronidase enzyme that breaks down HA, which has been modified to be more stable in the body. The idea behind the trial, generated by mouse model research published in 2012 by Hingorani’s team, is that using the enzyme to break down HA and lower the pressure inside the tumors will allow blood to penetrate and deliver cancer-killing drugs to their targets.