Final results of a phase Ib study of gemcitabine plus PEGPH20 in patients with stage IV previously untreated pancreatic cancer

• Published in: Journal of clinical oncology Vol. 33; no. 3_suppl; p. 359
• Main Authors: Hingorani, Sunil R., Harris, William Proctor, Beck, Joseph Thaddeus, Berdov, Boris A., Wagner, Stephanie Ann, Pshevlotsky, Eduard M., Tjulandin, Sergei, Gladkov, Oleg, Holcombe, Randall F., Jiang, Ping, Devoe, Craig E.
• Format: Journal Article
• Language: English
• Published: 20-01-2015
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2015.33.3_suppl.359

Abstract only
359
Background: Poor outcome in pancreatic cancer (PDA) has been associated with tumor stroma limiting access of chemotherapy drugs. PEGPH20 (PEG), PEGylated recombinant human hyaluronidase, which depletes hyaluronan (HA) in tumors, has demonstrated anti-tumor activity in preclinical PDA models. In a KPC model of PDA, PEG + gemcitabine (Gem) significantly prolonged survival compared to Gem alone. In Phase 1 PEG monotherapy studies, the MTD was 3µg/kg. The most common adverse events (AEs) were musculoskeletal events. Methods: This was a phase 1b study to determine the recommended phase 2 dose of PEG + Gem in patients (pts) with previously untreated Stage IV pancreatic cancer. PEG was given at 1, 1.6, or 3µg/kg IV twice weekly Wks 1–4 and weekly Wks 5–7, followed by 1 wk rest. Gem was given at 1000mg/m
2
IV once weekly for Wks 1–7, then 1 wk rest. Thereafter, PEG + Gem were given once weekly for 3 wks in 4-wk cycles. Dexamethasone was given pre and post PEG doses. Due to evolving SOC, the study was discontinued before initiation of the phase 2 randomization. Results: Twenty-eight pts were enrolled in the study. The majority of the patients (89%) had metastatic sites in the liver. Four, 4 and 20 pts received PEG at 1, 1.6 and 3µg/kg, respectively. The most common AEs related to PEG were muscle spasm (54%), myalgia (39%), arthralgia (29%), peripheral edema (29%), fatigue (25%), and extremity pain (18%). Median progression free survival (PFS) and overall survival (OS) were assessed and were 154 and 200 days, respectively. In an exploratory analysis, tumor biopsies from 17 pts were evaluated for HA levels (HA
high
or HA
low
). 6 pts were determined to have HA
high
tumors and 11 pts had HA
low
tumors. The median PFS and OS for HA
high
pts were 219 days (95% CI: 159-276) and 395 days (95% CI: 210-578). For HA
low
pts median PFS and OS were 108 (95% CI: 14-163) and 174 days (95% CI: 34-293). Conclusions: PEG + Gem is generally well tolerated in advanced pancreatic cancer and shows promising clinical activity, especially in pts with HA
high
tumors. ClinicalTrials.gov Identifier: NCT01453153.