Treatment Doubles Progression-free Survival in some PanCan Patients

Enzyme lowers pressure inside tumors, allows chemotherapy in

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.

Last September, the U.S. Food and Drug Administration granted fast-track status to Halozyme’s PEGPH20 program in pancreatic cancer, a designation that is designed to speed the development and review of drugs that fill an unmet need in treating serious medical conditions.

On Sunday, Hingorani will present results from 135 participants in the trial. So far, these preliminary data show that of the patients with high-HA tumors, those who received the experimental enzyme with their chemo experienced an average of 9.2 months of progression-free survival, more than double the 4.3 months of those with high HA who were treated with chemo but no enzyme. (For the patients with low HA, the enzyme didn’t seem to make a difference; these patients had only around five months of progression-free survival, on average, regardless of whether they had received the enzyme.)

The progression-free survival conferred on the high-HA patients by the experimental treatment is higher than the overall survival (a much more definitive survival measure) seen in a recently completed phase 3 trial of the combination chemotherapy — “which is what makes this so surprising,” Hingorani said.

Halozyme Therapeutics presented these preliminary results to analysts and investors in January. Reuters reported that CEO Helen Torley said PEGPH20 is “a blockbuster in waiting” and cited the wide range of solid tumors known to produce high levels of HA. Halozyme plans to begin a phase 3 trial of PEGPH20 in patients with high-HA pancreatic tumors early next year.

Halo 202’s preliminary results hold out the prospect of doubling the remaining life spans of many patients with metastatic pancreatic cancer, a disease in which survival after diagnosis is measured in months. But Hingorani stressed that these are still small numbers of patients and the results are still preliminary. “I look at this and I say, ‘OK, the hypothesis is still intact,’” said Hingorani, who has no personal financial interest in the study and said he has never owned any of Halozyme’s stock.

But he’s hopeful.

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