Halozyme Therapeutics Inc (HALO)

[Fred Kadiddlehopper]

Abstract 2321

http://www.europeancancercongress.org/Scientific-Programme/Abstract-search?abstractid=20793

Session title: Gastrointestinal Malignancies - Noncolorectal Cancer
Session type: Poster Session
Track: Gastrointestinal Malignancies
Abstract number: 2321
Abstract title:
High response rate and progression free survival with PEGylated recombinant human hyaluronidase added to Nab-Paclitaxel/Gemcitabine in stage IV previously untreated pancreatic cancer patients with high-HA tumors: Interim results of a randomized Phase 2 study

S. Hingorani(1), W. Harris(2), A. Hendifar(3), A. Bullock(4), X. Wu(5), Y. Huang(5), P. Jiang(6), D. Von Hoff(7)

(1)Fred Hutchinson Cancer Research Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
(2)University of Washington School of Medicine, Division of Oncology, Seattle, WA, USA
(3)Cedars Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA
(4)Beth Israel Deaconess Medical Center, Division of Hematology-Oncology, Boston, MA, USA
(5)Halozyme Therapeutics, Biostatistics & Data Management, San Diego, CA, USA
(6)Halozyme Therapeutics, Translational & Clinical Science, San Diego, CA, USA
(7)Clinical Translational Research Division, Translational Genomics Research Institute, Phoenix, AZ, USA
Background: Poor outcomes in pancreatic cancer (PDA) are associated in part with tumor stroma limiting chemotherapy perfusion. PDAs express high levels of hyaluronan (HA), which contributes to elevated interstitial pressures. PEGylated recombinant human hyaluronidase, PEGPH20, depletes HA in tumors. In a Phase 1b study of PEGPH20 with gemcitabine (Gem), patients (pts) whose tumors were HA-high had improved ORR, PFS and OS compared to those with tumors that were HA-low.

Methods: This is an ongoing Phase 2 open-label, randomized study of PEGPH20+nab-paclitaxel (Nab)+Gem (PAG) vs. Nab+Gem (AG) in previously untreated pts with Stage IV PDA. Pts receive 3µg/kg twice weekly (Cycle 1) and then weekly (Cycle 2+) PEGPH20 in combination with standard dosing of AG. HA status was tested retrospectively. Primary endpoint is PFS. Secondary endpoints include ORR, OS and Safety. Due to a temporary clinical hold, ORR is from data through April 2014 and PFS is data through December 2014.

Endpoint/Population PAG AG P-value
ORR
N=135 25/74 (34%) 14/61 (23%) 0.17
HA-high N=34 12/17 (71%) 5/17 (29%) 0.02
HA-low N=28 9/18 (50%) 5/10 (50%) 0.94
PFS
ITT N=135 42/74; 5.7 months 39/61; 5.2 months 0.10
HA-high N=48 12/25; 9.2 months 15/23; 4.3 months 0.03
HA-low N=58 22/36; 4.8 months 15/22; 5.6 months 0.81
Results: A total of 146 pts were enrolled of which 135 pts received at least one dose of the study drug. The mean age of the pt was 65.1yrs (Range 29–83yrs). Ninety-three percent of pts who received at least one dose of the study drug had a KPS of ≥80. The most common AEs related to study drugs (PAG vs. AG) were fatigue (68% vs. 69%), nausea (55% vs. 44%), anemia (42% vs. 53%) peripheral edema (58% vs. 31%) and muscle spasms (57% vs. 5%). There was an imbalance of thromboembolic (TE) events (PAG vs. AG) with 42% vs. 25% of subjects having at least one TE event. Overall RR and PFS are shown in the table.

Conclusions: PEGPH20 + Nab/Gem is generally well tolerated in advanced PDA. Patients with HA-high tumors receiving PAG had greater ORR and longer PFS than HA-high patients receiving AG. Overall survival will be presented at the time of the meeting.

ClinicalTrials.gov Identifier NCT01839487.

Conflict of interest: Corporate-sponsored Research: Sunil Hingorani, William Harris, Andrew Hendifar, Andrea Bullock and Daniel Von Hoff are investigators on the study. Other Substantive Relationships: Wilson Wu, Ya Huang, and Ping Jiang are employees of Halozyme Therapeutics, the study sponsor.

Keywords:
pancreatic cancer
High-HA Tumors
PEGPH20
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