Results of a phase 3 study comparing pegvorhyaluronidase alfa, or PEGPH20, with placebo both in combination with first-line gemcitabine-based chemotherapy in patients with metastatic, hyaluronan-high pancreatic ductal adenocarcinoma (PDAC) showed no significant difference in overall survival (OS) between the 2 study arms. The findings from this study were reported at the 2020 Gastrointestinal Cancers Symposium held in San Francisco, California.1
Pegvorhyaluronidase alfa is a pegylated recombinant human hyaluronidase that degrades hyaluronan, a component of the tumor microenvironment in PDAC.
Results of preclinical studies, as well as a phase 2 study, have shown promising activity for PEGPH20 in the setting of metastatic PDAC.2 One of the rationales for combining PEGPH20 with other agents is to facilitate access of the drugs to the tumor.
Furthermore, a subset of pancreatic cancers are characterized by a tumor microenvironment that is enriched in hyaluronan (ie, hyaluronan-high), and can be identified using a commercially available assay.
In this randomized, double-blind, placebo-controlled phase 3 study (HALO 109-301; ClinicalTrials.gov Identifier: NCT02715804), 494 patients with previously untreated metastatic hyaluronan-high PDAC were randomly assigned in a 2:1 ratio to receive first-line chemotherapy with gemcitabine and nab-paclitaxel in combination with either PEGPH20 or placebo. The primary study endpoint was OS, with progression-free survival (PFS), objective response rate (ORR), and safety included as secondary study endpoints.
Median OS, assessed following 330 deaths, was 11.2 months for patients receiving chemotherapy plus PEGPH20 and 11.5 months for those treated with chemotherapy plus placebo (hazard ratio [HR], 1.00; 95% CI, 0.80–1.27; P =.97). Furthermore, a comparison of median PFS in the 2 study arms showed no difference (ie, 7.1 months in both arms), and confirmed ORRs were 34% and 27% for those receiving chemotherapy plus PEGH20 or chemotherapy plus placebo, respectively.
Regarding safety, respective rates of selected grade 3 or higher adverse events in patients receiving PEGPH20 compared with placebo included the following: neutropenia (44% vs 47%), thrombocytopenia (21% vs 16%), fatigue (16% vs 10%), thromboembolic events (6% vs 7%), bleeding events (5% vs 2%), and musculoskeletal events (13% vs 5%).
Disclosures: This study was funded by Halozyme. Some of the study authors reported financial relationships with pharmaceutical companies. For a full list of disclosures, please refer to the study abstract.
- Tempero MA, Van Cutsem E, Sigal D, et al. HALO 109-301: A randomized, double-blind, placebo-controlled, phase 3 study of pegvorhyaluronidase alfa (PEGPH20) + nab-paclitaxel/gemcitabine (AG) in patients (pts) with previously untreated hyaluronan (HA)-high metastatic pancreatic ductal adenocarcinoma (mPDA). J Clin Oncol. 2020;38(suppl 4):Abstract 638.
- Hingorani SR, Zheng L, Bullock AJ, et al. HALO 202: Randomized phase II study of PEGPH20 plus nab-paclitaxel/gemcitabine versus nab-paclitaxel/gemcitabine in patients with untreated, metastatic pancreatic ductal adenocarcinoma. J Clin Oncol. 2018;36:359-366.
This article originally appeared on Cancer Therapy Advisor