On October 22, 2018 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported the presentation of data from two clinical trials for PEGPH20 (pegvorhyaluronidase alfa) in patients with advanced pancreas and metastatic breast cancer (Press release, Halozyme, OCT 22, 2018, View Source [SID1234530030]). The presentations were made at the annual European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress, taking place October 19-23 in Munich. PEGPH20 is Halozyme’s proprietary PEGylated recombinant human hyaluronidase enzyme that degrades hyaluronan (HA), a glycosaminoglycan or naturally occurring sugar in the body. HA accumulates in many solid tumors, potentially impeding the immune response and the access of anti-cancer therapies. PEGPH20 is being developed as an investigational new drug for the treatment of advanced pancreas cancer, specifically in patients with tumors that accumulate HA, referred to as HA-high.
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"These data reinforce the potential for PEGPH20 in combination with chemotherapy in these well-defined patient populations. It adds to the supportive evidence that suggests PEGPH20 could play a critical role in degrading tumor HA, allowing greater penetration of chemotherapy and improved access of the immune system into the tumor," said Dr. Helen Torley, president and chief executive officer of Halozyme. "PEGPH20 may provide a unique targeted approach for patients with late-stage cancers where new treatment options are needed."
Poster Presentations of PEGPH20 Clinical Studies at ESMO (Free ESMO Whitepaper) 2018
Abstract 5965/730P – A pilot study of gemcitabine, nab-paclitaxel, PEGPH20 and rivaroxaban for advanced pancreatic adenocarcinoma: interim safety and efficacy analysis
K. Yu, Memorial Sloan-Kettering Cancer Center, et al.
This investigator sponsored study has enrolled 60 patients with advanced pancreatic adenocarcinoma (PDAC), 42 patients without prior thromboembolic events (TE) in cohort 1 and 18 patients with prior TE in cohort 2. Patients received PEGPH20 (3 ug/kg, the same dose as is being evaluated in HALO-301), plus the standard dose and schedule for nab-paclitaxel (125 mg/m2), and gemcitabine (1000 mg/m2), plus rivaroxaban (15 mg PO BID for 21 days induction, then 20 mg PO QD), an oral anticoagulant that has been shown to reduce TE in patients receiving chemotherapy. The primary objective was the rate of symptomatic TE events, and the secondary objectives included PFS, OS and major bleeding rate.
All 60 patients are evaluable for safety and efficacy. Two (3%) grade 3/4 TE events occurred (one in each cohort), and two grade 3 GI hemorrhages; these AEs resolved with supportive treatment. There were three (5%) complete responses, 28 (47%) partial responses, 20 (33%) stable disease responses, and 9 (15%) progressive disease/non-evaluable responses. Median PFS is 7.0 months across both cohorts, and median overall survival has not been reached. Efficacy and safety are similar for patients with and without prior TE. Tissue biopsies have been collected to evaluate response by HA level but the analysis is not yet completed.
Abstract 5999/311P – Early results from an Open-label Phase 1b/2 study of eribulin mesylate (EM) + pegvorhyaluronidase alpha (PEGPH20) combination for the treatment of patients with HER2-negative, high-hyaluronan (HA) metastatic breast cancer (MBC)
M. Shum, The Oncology Institute Whittier, et al.
The Phase 1b portion of the study enrolled 14 patients with HER2 negative metastatic breast cancer without regard for HA status. Patients were treated with IV PEGPH20 plus eribulin mesylate (HALAVEN), a microtubule inhibitor approved for the treatment of metastatic breast cancer in patients previously treated with up to two lines of systemic anticancer therapy. Two different dose-levels of PEGPH20 (3ug/kg and 1.6ug/kg) were tested in combination with 1.4 mg/m2 EM. The data cut-off date for this analysis was February 2018. The median number of 21-day treatment cycles in this trial was six. No complete responses were reported, four (28.6%) patients had a partial response and three (21%) had stable disease. Drug related treatment emergent adverse events (TEAEs) occurred in 86% of patients, with 79% of patients experiencing grade 3 or higher TEAEs. There were three serious adverse events, and the overall safety profile for PEGPH20 + eribulin mesylate was in line with previous observations, with no new safety signals identified. As a result of dose limiting toxicities at the higher dose,1.6ug/kg was determined to be the appropriate dose for this combination. An additional response was confirmed following the data cutoff, increasing the overall response rate to 36%. The overall response rate is encouraging and the PEGPH20 + eribulin mesylate combination warrants further investigation.
About PEGPH20
PEGPH20 is an investigational PEGylated form of Halozyme’s proprietary recombinant human hyaluronidase enzyme under clinical development for the potential systemic treatment of tumors that accumulate hyaluronan (HA). PEGPH20 targets and degrades hyaluronan, a glycosaminoglycan or naturally occurring sugar in the body. HA accumulates in many solid tumors, potentially constricting blood vessels, impeding the immune response and the access of anti-cancer therapies. PEGPH20 is being studied in a Phase 3 trial in patients with late stage HA-high pancreas tumors.
