Purpose: This Phase 1b study evaluated the safety and tolerability of PEGylated human recombinant hyaluronidase (PEGPH20) in combination with gemcitabine (Gem), and established a Phase 2 dose for patients with untreated Stage IV metastatic pancreatic ductal adenocarcinoma (PDA). Objective response rate and treatment efficacy using biomarker and imaging measurements were also evaluated. Experimental Design: Patients received escalating intravenous doses of PEGPH20 in combination with Gem using a standard 3+3 dose-escalation design. In Cycle 1 (8 weeks), PEGPH20 was administrated twice weekly for 4 weeks, then once weekly for 3 weeks; Gem was administrated once weekly for 7 weeks, followed by 1 week off treatment. In each subsequent 4-week cycle, PEGPH20 and Gem were administered once weekly for 3 weeks, followed by 1 week off. Dexamethasone (8 mg) was given pre- and post-PEGPH20 administration. Several safety parameters were evaluated. Results: Twenty-eight patients were enrolled and received PEGPH20 at 1.0 (n=4), 1.6 (n=4), or 3.0 µg/kg (n=20), respectively. The most common PEGPH20-related adverse events were musculoskeletal and extremity pain, peripheral edema, and fatigue. The incidence of thromboembolic events was 29%. Median progression-free survival (PFS) and overall survival (OS) were 5.0 and 6.6 months, respectively. In 17 patients evaluated for pre-treatment tissue hyaluronan (HA) levels, median PFS and OS were 7.2 and 13.0 months for "high"-HA patients (n=6), and 3.5 and 5.7 months for "low"-HA patients (n=11), respectively. Conclusion: PEGPH20 in combination with Gem was well tolerated and may have therapeutic benefit in patients with advanced PDA, especially in those with high-HA tumors.
- Received September 3, 2015.
- Revision received December 18, 2015.
- Accepted December 24, 2015.
- Copyright © 2016, American Association for Cancer Research.