Date: 2016-06-04
Type of information: Results
phase: 2
Announcement: results
Company: Halozyme Therapeutics (USA - CA)
Product: PEGPH20
Action
mechanism: enzyme. PEGPH20 is an investigational PEGylated form of Halozyme's proprietary recombinant human hyaluronidase under development for the systemic treatment of tumors that accumulate hyaluronan. FDA granted orphan drug designation to PEGPH20 for treatment of pancreatic cancer and fast track for PEGPH20 in combination with gemcitabine and nab-paclitaxel for the treatment of metastatic pancreatic cancer. Additionally, the European Commission designated investigational drug PEGPH20 an orphan medicinal product for the treatment of pancreatic cancer.
Disease: pancreatic cancer
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: Study 202 (Halo 109-202) is a phase 2 multi-center, randomized clinical trial evaluating investigational new drug PEGPH20 as a first-line therapy for potential treatment of patients with metastatic pancreatic cancer. The primary outcome of the trial is to measure improvement in progression-free survival in patients receiving investigational new drug PEGPH20 in combination with gemcitabine and nab-paclitaxel compared to gemcitabine and nab-paclitaxel alone. A second primary endpoint will assess the thromboembolic event rate in the PEGPH20 treatment arm. Secondary endpoints also include objective response rate and overall survival. (NCT01839487)
Latest
news: * On June 4, 2016, Halozyme Therapeutics announced results from a final analysis of 135 metastatic pancreatic cancer patients who were treated in Stage One of HALO 109-202, a phase 2 clinical study of its investigational new drug PEGPH20 in combination with Abraxane® (nab-paclitaxel) and gemcitabine (PAG arm) as compared to Abraxane® and gemcitabine alone (AG arm). This final analysis of secondary and exploratory endpoints was conducted using the Ventana companion diagnostic to retrospectively identify high levels of hyaluronan (HA). The key results based on a February 2016 data cut-off showed in the HA-high patient population: Median progression-free survival (PFS) was 9.2 months in the PAG arm versus 6.0 months in the AG arm, hazard ratio (HR) with a 95 percent confidence interval (CI): 0.46 (0.15, 1.40); Prior interim analyses were based on patient follow up through December 2014. Results announced today include 14 months of additional follow up through February 2016. Stage One of HALO 202 enrolled a total of 146 patients between May 2013 to July 2014. The study was placed on clinical hold from April to July 2014 during which time PEGPH20 was discontinued while patients in both arms continued to receive treatment with ABRAXANE and gemcitabine alone. Stage Two enrolled a total of 133 patients as of February 2016 and Halozyme remains blinded to the overall efficacy. The company projects to report mature PFS and ORR results from Stage Two late in the fourth quarter. * On May 31, 2015, Halozyme Therapeutics announced interim findings from the ongoing phase 2 clinical study of its investigational new drug PEGPH20 for the potential treatment of patients with metastatic pancreatic cancer. The interim data was presented at the American Society of Clinical Oncology annual meeting in an oral presentation by Principal Investigator Sunil Hingorani, M.D., Ph.D., Associate Member of the Fred Hutchinson Cancer Research Center and Associate Professor at University of Washington School of Medicine. The trial included 135 treated patients in stage 1, of whom a total of 44 patients -- 23 receiving PEGPH20 in combination with Abraxane® and gemcitabine (PAG treatment arm) and 21 receiving Abraxane® and gemcitabine alone (AG treatment arm) -- had available biopsies that were determined in a retrospective analysis to have high levels of hyaluronan (HA). PEGPH20 targets HA to help improve cancer therapy access to tumor cells. Results reported include: A more than doubling of median progression-free survival of 9.2 months versus 4.3 months in high HA patients treated with PAG vs. AG (hazard ratio of 0.39; p-value of 0.05); A TE event rate of 13 percent in 38 patients treated with PAG versus 18 percent in 17 patients receiving AG; Halozyme previously announced it plans to proceed in Q1 2016 with a phase 3 clinical study (Study 301) of PEGPH20 in patients with metastatic pancreatic cancer, using a design allowing for potential marketing application based on either progression-free survival or overall survival.
Overall response rate (ORR) of 50 percent, including one complete response in the PAG arm versus 33 percent and all partial responses in the AG arm;
Median duration of response (DoR) of 8.1 months in the PAG arm versus 3.7 months in the AG arm;
The exploratory analysis of median overall survival (OS) was similar between the treatment arms -- 11.8 months vs. 10.9 months in the PAG vs. AG arms respectively. Factors potentially having an impact on these results include less aggressive disease among patients in the AG arm and a greater than 40 percent discontinuation rate of PEGPH20 treatment at the time of the clinical hold, resulting in all patients receiving AG alone in both arms;
The rate of thromboembolic (TE) events reduced from 43 percent to 9 percent in the PAG arm and from 25 percent to 6 percent in the AG arm with the introduction of prophylaxis with low molecular weight heparin (enoxaparin) from Stage One to Stage Two of the study.
A more than doubling of overall response rate of 52 percent versus 24 percent (p-value of 0.038) and a duration of response of 8.1 months compared to 3.7 months in high HA patients treated with PAG versus AG;
In the 30 high HA patients (15 PAG treatment arm versus 15 AG treatment arm) who were evaluated for response prior to the April 2014 clinical hold and subsequent PEGPH20 treatment discontinuation, the overall response rate was 73 percent versus 27 percent (p-value of 0.01), respectively, consistent with findings presented in January;
A trend toward improvement in median overall survival of 12 months compared to 9 months in high HA patients treated with PAG versus AG (hazard ratio of 0.62) despite discontinuation of PEGPH20 in more than half of the PAG-treated patients at the time of the clinical hold in April 2014.
Data was also presented on the rate of thromboembolic (TE) events in 55 patients treated in stage 2 of the trial, which is currently randomizing patients at a 2:1 ratio of PAG versus AG. Stage 2 began after a protocol amendment in July 2014, excluding patients at high risk of TE events and adding prophylaxis with low molecular weight heparin (enoxaparin) to all patients in both treatment arms. Reported results included:
In the 20 PAG patients receiving 1 mg/kg/day of enoxaparin, no TE events have been reported to date.
