PEGH20 Combination Misses Primary Endpoint in Phase III HALO-301 Trial

The combination of pegylated human hyaluronidase (PEGH20) with gemcitabine and nab-paclitaxel (Abraxane) failed to improve the median overall survival (OS) in patients with metastatic pancreatic cancer, missing the primary endpoint of the phase III HALO-301 trial (NCT02715804), Halozyme Therapeutics, Inc. reported in a press release.¹

Compared to the arm that received gemcitabine and nab-paclitaxel alone, which had a median OS of 11.5 months, the PEGPH20 combination arm had a median OS of 11.2 months. The hazard ratio was 1.00 and theP-value was 0.9692.

In addition to missing the primary endpoint, the combination arm also did not improve progression-free survival (PFS) or duration of response (DOR), 2 secondary endpoints of the trial.¹The other secondary endpoints were objective response rate and the number of study participants with treatment-emergent adverse events. Data related to these endpoints have not yet been reported.

PEGPH20 was previously granted an FDA orphan drug designation for pancreatic cancer based on earlier phases of the study.²HALO-301 has since been stopped due to the poor efficacy of the combination.¹

Helen Torley, MD, president and CEO, Halozyme announced the discontinuation of the study in the press release, stating, “Patients in both treatment arms of the HALO-301 trial surpassed the published median overall survival rates from the pivotal registration study of Abraxane plus gemcitabine as first-line therapy for metastatic pancreas cancer, published in 2013. Based on the lack of benefit over standard-of-care in this study, which performed well versus published data, we will be discontinuing PEGPH20 clinical development.”

Torley considered the trial to be well designed and executed. Previously untreated patients with hyaluronan-high stage IV pancreatic ductal adenocarcinoma (PDAC) were randomized 2:1 to either PEGPH20 with gemcitabine and nab-paclitaxel, or gemcitabine and nab-paclitaxel alone. In the combination group, PEGPH20 or matching placebo was given intravenously, twice weekly during week 1 to 3 followed by a week of rest in week 4. In the gemcitabine/nab-paclitaxel arm, patients were given 125 mg/m²of gemcitabine and 1000 mg/m²of nab-paclitaxel intravenously, once weekly for weeks 1 to 3. Both groups would discontinue treatment in the case of disease progression, unacceptable toxicity, death, or withdrawal of consent.

Those enrolled in the trial must have had stage IV PDAC with histological or cytological confirmation of PDAC, hyaluronan-high disease, and radiographic confirmation of stage IV PDAC. Patients were also required to have an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1, and a life expectancy of at least 3 months.

Individuals with deep vein thrombosis, pulmonary embolism, or other thromboembolic conditions, and those with central nervous system involvement or brain metastases, New York Heart Association Class III or IV cardiac disease, clinically significant pre-existing carotid artery disease, or severe viral infections were excluded from the trial. Patients were also unable to enroll if they were previously treated with radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease.

“This well-designed and the well-executed study did not have the outcome that we or the study participants wanted or expected. I would like to extend a heartfelt thank you to all those who supported and who made this study possible…,” said Torley.

In another press release, Halozyme Therapeutics, Inc announced its exit from the oncology space, planning to close its oncology operations in addition to discontinuing the development of PEGPH20.³

References

1. Halozyme Announces HALO-301 Phase 3 Study Fails To Meet Primary Endpoint [press release]. San Diego: Halozyme Therapuetics, Inc; November 4, 2019. https://bit.ly/2JOixgG. Accessed November 4, 2019.
2. Halozyme Receives Orphan Drug Designation For PEGylated Recombinant Human Hyaluronidase PH20 For Pancreatic Cancer [press release]. San Diego: Halozyme Therapuetics, Inc; October 3, 2014. https://bit.ly/33d3N2w. Accessed November 4, 2019.
3. Halozyme Announces Actions To Focus Strategy On ENHANZE® Drug Delivery Technology [press release]. San Diego: Halozyme Therapuetics, Inc; November 4, 2019.https://bit.ly/2JOCa8l. Accessed November 4, 2019.