The addition of the investigational drug PEGPH20 to standard first-line chemotherapy significantly prolonged PFS among patients with stage IV metastatic pancreatic cancer, according to study results released by the agent’s manufacturer.
Topline results of the randomized, phase 2 HALO 202 study showed the addition of PEGPH20 (Halozyme Therapeutics) to nanoparticle albumin-bound paclitaxel (Abraxane, Celgene) — often called nab-paclitaxel — and gemcitabine extended PFS in all evaluable patients, including those with high levels of hyaluronan. Among this subgroup, median PFS was 8.6 months among those assigned the PEGPH20 regimen, compared with 4.5 months among those assigned the control regimen.
PEGPH20 is an investigational pegylated form of a proprietary recombinant human hyaluronidase designed to treat tumors that accumulate hyaluronan. Hyaluronan — a component of the tumor microenvironment — often is found in higher concentrations around cancer cells. This can constrict blood vessels and potentially limit access of other therapies.
An estimated 35% to 40% of patients with pancreatic cancer have high expression of hyaluronan, and they tend to have poorer outcomes.
“[The data] confirm for the first time in a randomized phase 2 trial using the current standard of care that a biopsy-based biomarker for hyaluronan content can potentially identify patients who will have a meaningfully greater response when PEGPH20 is added to their treatment,” Sunil R. Hingorani, MD, PhD, member of the clinical research division at Fred Hutchinson Cancer Research Center, professor at University of Washington School of Medicine and principal investigator of the HALO 202 study, said in a Halozyme-issued press release. “The analysis suggests statistically significant and clinically important progress in this very difficult-to-treat cancer. The median PFS is a notable increase over the current standard of care.”
A second stage of the study achieved its primary endpoint by demonstrating a reduction in the rate of thromboembolic events among PEGPH20–treated patients.
“These findings confirm our confidence in the development of PEGPH20 in this difficult-to-treat cancer,” Helen Torley, MB, ChB, MRCP, president and CEO of Halozyme, said in the press release. “We are pleased by the overall consistency of both the efficacy and safety data, which are supportive of our ongoing phase 3 clinical trial.”
That phase 3 trial, HALO 301, is underway at more than 160 sites around the world. Primary endpoints are PFS and OS among patients who receive PEGPH20 in combination with nab-paclitaxel and gemcitabine, compared with those who receive nab-paclitaxel and gemcitabine alone. Secondary endpoints include objective response rate and OS.
The FDA granted orphan drug designation to PEGPH20 for the treatment of pancreatic cancer. The agency also granted fast track designation to use of the agent in combination with nab-paclitaxel and gemcitabine for patients with metastatic pancreatic cancer.