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.
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.
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: 730P
|Variable||Cohort 1||Cohort 2||Overall|
|Safety||n = 28||n = 14||n = 42|
|TE Events||1 (3.6%)||0 (0%)||1 (2.4%)|
|Major Bleeding||2 (7.1%)||0 (0%)||2 (4.8%)|
|Complete Response||1 (3.6%)||1 (7.1%)||2 (4.8%)|
|Partial Response||14 (50.0%)||5 (35.7%)||19 (45.2%)|
|Stable Disease||8 (28.6%)||7 (50.0%)||15 (35.7%)|
|Progressive Disease||2 (7.1%)||0 (0%)||2 (4.8%)|
|Not Evaluable||3 (10.7%)||1 (7.1%)||4 (9.5%)|
|PFS||6.0 mo||8.0 mo||7.0 mo|
|OS||Not Reached||Not Reached||Not Reached|
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
Legal entity responsible for the study
Memorial Sloan Kettering Cancer Center.
Halozyme Therapeutics, Inc.
All authors have declared no conflicts of interest.