Intratumoral and subcutaneous injection of HVJ-E (GEN0101) for metastatic castration-resistant prostate cancer: Open-label, phase I, dose escalation study.

Abstract

e16511 Background: Inactivated Sendai virus particles (hemagglutinating virus of Japan envelope (HVJ-E)) have a novel antitumor effect: HVJ-E fused to prostate cancer cells via cell surface receptor causes apoptosis of prostate cancer cells in vitro and in vivo. HVJ-E also induces antitumor immunity by activating natural killer (NK) cells and cytotoxic T cells and suppressing regulatory T cells in vivo. We conducted an open-label, phase I, dose-escalation study in patients with castration-resistant prostate cancer (CRPC) to determine the safety and efficacy of intratumoral and subcutaneous injection of HVJ-E (GEN0101). Methods: Patients with CRPC who were resistant to standard of care or could not receive standard of care were eligible. GEN0101 was injected directly into the prostate on day 1 and subcutaneously on days 5, 8 and 12 in two 28-day treatment cycles using a modified 3+3 dose-escalation design to determine the recommended dose of GEN0101. The primary end points were to evaluate safety and tolerability of GEN0101 and determine the recommended dose. The secondary end points were to analyze antitumor effect and tumor immunity. The study is registered at UMIN Clinical Trials Registry, number UMIN000017092. Results: Of the 9 patients treated, 3 received 30,000mNAU of GEN0101 and 6 received 60,000mNAU. There were no dose-limiting toxicities, and the recommended dose of GEN0101 was defined as 60,000mNAU. Radiographically, one patient had stable disease and 2 had progressive disease in the low-dose group, and 5 patients had stable disease and one had progressive disease in the high-dose group. Four patients in high dose group had reductions in lymph node metastasis after 2 treatment cycles. Final PSA increase rates in high-dose group were more suppressed than those in low-dose group. NK cell activity was enhanced in 2 patients (66%) in low-dose group and 5 patients (83%) in high-dose group, Serum interleukin-6, and IFN-γ levels were not affected by GEN0101 treatment. Conclusions: Intratumoral and subcutaneous injections of GEN0101 were well tolerated and feasible. Antitumor effect in lymph node metastasis were observed in CRPC patients. It is necessary to test whether the treatment with GEN0101 improves the survival of CRPC patients. Clinical trial information: UMIN000017092.