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Clinical Trial
. 2020 May;111(5):1692-1698.
doi: 10.1111/cas.14366. Epub 2020 Mar 19.

Intratumoral and s.c. injection of inactivated hemagglutinating virus of Japan envelope (GEN0101) in metastatic castration-resistant prostate cancer

Kazutoshi Fujita  1 , Taigo Kato  1 , Koji Hatano  1 , Atsunari Kawashima  1 , Takeshi Ujike  1 , Motohide Uemura  1 , Ryoichi Imamura  1 , Koji Okihara  2 , Osamu Ukimura  2 , Tsuneharu Miki  2 , Toshihiro Nakajima  3 , Yasufumi Kaneda  4 , Norio Nonomura  1
Affiliations
Clinical Trial

Intratumoral and s.c. injection of inactivated hemagglutinating virus of Japan envelope (GEN0101) in metastatic castration-resistant prostate cancer

Kazutoshi Fujita et al. Cancer Sci. 2020 May.

Abstract

Inactivated hemagglutinating virus of Japan envelope (HVJ-E) has an antitumor effect and tumor immunity. We undertook 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 s.c. injection of HVJ-E (GEN0101). Patients with CRPC, who were resistant to or unable to receive standard of care, were included. GEN0101 was injected directly into the prostate and s.c. in two 28-day treatment cycles. The primary end-points were to evaluate the safety and tolerability of GEN0101 and determine its recommended dose. The secondary end-points were to analyze the antitumor effect and tumor immunity. Three patients received 30 000 mNAU GEN0101 and 6 received 60 000 mNAU. There was no dose-limiting toxicity, and the recommended dose of GEN0101 was defined as 60 000 mNAU. Radiographically, 1 patient had stable disease and 2 had progressive disease in the low-dose group, whereas 5 patients had stable disease and 1 had progressive disease in the high-dose group. Three patients in the high-dose group showed reduction in lymph node metastasis. Prostate-specific antigen increase rates in the high-dose group were suppressed more than those in the low-dose group. Natural killer cell activity was enhanced in 2 patients of the low-dose group and in 5 patients in the high-dose group. In conclusion, intratumoral and s.c. injections of GEN0101 were well-tolerated and feasible to use. The study is registered with the UMIN Clinical Trials Registry (no. UMIN000017092).

Keywords: NK cell; Sendai virus; antitumor effect; castration-resistant prostate cancer; phase I clinical study.

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Conflict of interest statement

Toshihiro Nakajima is the CEO of GenomIdea. Yasufumi Kaneda is a stock‐holder (0.3%) of GenomIdea. The other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Patients with castration‐resistant prostate cancer underwent transrectal ultrasound‐guided injection of GEN0101 (inactivated hemagglutinating virus of Japan envelope [HVJ‐E]) into the prostate on day 1, followed by s.c. injection of HVJ‐E on days 5, 8, and 12. Patients underwent 2 cycles of GEN0101 treatment
Figure 2
Figure 2
Diagram of patients with castration‐resistant prostate cancer who were enrolled in the low‐dose (30 000 mNAU GEN0101) or high‐dose (60 000 mNAU GEN0101) treatment groups. HVJ‐E, inactivated hemagglutinating virus of Japan envelope
Figure 3
Figure 3
Changes in serum prostate‐specific antigen (PSA) levels from the baseline in patients with castration‐resistant prostate cancer who were enrolled in the low‐dose (LD; 30 000 mNAU GEN0101) or high‐dose (HD; 60 000 mNAU GEN0101) treatment group. A, Low‐dose group (n = 3). B, High‐dose group (n = 6)
Figure 4
Figure 4
Change in lymph node metastasis during the GEN0101 treatment in patients with castration‐resistant prostate cancer. A, Change in lymph node metastasis in 3 patients in the high‐dose group (HD; 60 000 mNAU GEN0101). B, Computed tomography image of lymph node metastasis (arrowheads). HVJ‐E, inactivated hemagglutinating virus of Japan envelope
Figure 5
Figure 5
Changes in natural killer cell activity from baseline in patients with castration‐resistant prostate cancer who received low‐dose (LD; 30 000 mNAU) or high‐dose (HD; 60 000 mNAU) GEN0101
See this image and copyright information in PMC

References

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