730P - A pilot study of gemcitabine, nab-paclitaxel, PEGPH20 (PAG) and rivaroxaban for advanced pancreatic adenocarcinoma: Interim safety and efficacy analysis

Abstract

Background: PEGPH20 (P) degrades hyaluronan (HA), a key component of pancreatic adenocarcinoma (PDAC) tumor microenvironment, leading to reduction of tumor interstitial pressure, decompression of tumor blood vessels and improvement in delivery of chemotherapeutics. A prior study of P with chemotherapy in PDAC (HALO-202) found an increased risk of thromboembolic (TE) events, 43%, effectively reduced with enoxaparin prophylaxis. Rivaroxaban (R) is a safe and effective oral anticoagulant for treating cancer-related TE. Methods: Patients considering frontline therapy for advanced PDAC and with KPS ≥ 70 were studied. 28 patients without prior TE (cohort 1) and 14/28 planned patients with prior TE (cohort 2) were enrolled. Patients received treatment with PAG (P; 3 µg/kg IV 2x/wk x 3 wks in C1, then 1x/wk x 3 wks in C2+, plus standard dose and schedule nab-paclitaxel and gemcitabine (AG)) every 28 days, with R (15 mg twice daily for 21 days, followed by 20 mg once daily). Primary endpoint is TE event rate. Secondary endpoints include PFS, OS, major bleeding rate and RR. Results: All 42 patients are evaluable for efficacy and safety. Key patient characteristics: median age = 61, M/F 22/20, stage III/IV 5/37. Median follow-up is 10.9 mo. One (2.4%) grade 4 TE event occurred. Two grade 3 GI hemorrhages occurred, both resolved with supportive measures. Best responses: complete response 2 (4.8%), partial response 19 (45.2%), stable disease 15 (35.7%), progressive disease 2 (4.8%), and overall disease control rate of 85.7%. Median PFS is 7.0 mo, mOS has not been reached. Safety and efficacy are similar across both cohorts (see Table).Table: 730PVariableCohort 1Cohort 2OverallSafetyn = 28n = 14n = 42TE Events1 (3.6%)0 (0%)1 (2.4%)Major Bleeding2 (7.1%)0 (0%)2 (4.8%)EfficacyComplete Response1 (3.6%)1 (7.1%)2 (4.8%)Partial Response14 (50.0%)5 (35.7%)19 (45.2%)Stable Disease8 (28.6%)7 (50.0%)15 (35.7%)Progressive Disease2 (7.1%)0 (0%)2 (4.8%)Not Evaluable3 (10.7%)1 (7.1%)4 (9.5%)PFS6.0 mo8.0 mo7.0 moOSNot ReachedNot ReachedNot Reached Open table in a new tab Conclusions: Interim analysis shows R is safe and effectively prevents TE events in patients receiving PAG. Responses and disease control rate are encouraging in this tumor HA-level unselected patient population. Updated safety and efficacy data will be reported. Clinical trial identification: NCT02921022. Legal entity responsible for the study: Memorial Sloan Kettering Cancer Center. Funding: Halozyme Therapeutics, Inc. Disclosure: All authors have declared no conflicts of interest.