A phase I dose-escalation, safety/tolerability, and preliminary efficacy study of the intratumoral administration of GEN0101 in patients with advanced melanoma

Abstract

Despite recent advance in immunotherapy agents, safe new therapies that enhance the effects of immune checkpoint inhibitors are still required to develop. We previously demonstrated that hemagglutinating virus of Japan-envelope (HVJ-E) induced not only direct tumor cell death but also antitumor immunity through the activation of T and natural killer (NK) cells, thereafter, developed a manufacturing process of HVJ-E (GEN0101) for clinical use. We here performed a phase Ia clinical trial of intratumoral GEN0101 administration in six patients with stage IIIC or IV malignant melanoma. The primary aim was to evaluate the safety and tolerability of GEN0101, and the secondary aim was to examine the objective tumor response. Patients were separated into two groups (n = 3 each) and received a low dose of 30,000 and high dose of 60,000 mNAU of GEN0101. All patients completed a two-week follow-up evaluation without severe adverse events. The overall response rate was 33% (2 of 6), with 2 partial responses in the high-dose group and 2 with stable disease, and 2 with progressive disease in the low-dose group. Local complete or partial responses were observed in 11 of 18 (61%) target lesions. One patient demonstrated shrinkage of lung metastases after the treatment. The activity of NK cells and interferon-γ levels were increased in the circulation, indicating augmentation of antitumor immunity by GEN0101. This trial showed not only the safety and tolerability but also the significant antitumor effect of GEN0101, suggesting that GEN0101 might be a promising new drug for patients with advanced melanoma.

Recent advances in immunotherapy and its combination therapies for advanced melanoma: a review

“…In the Phase I clinical trial, HVJ-E (GEN0101) with 30000 mNAU and 60000 mNAU was administered to patients with advanced melanoma without dose-limiting toxicity. The anti-tumor activity increased in a dose-dependent manner, and the target lesion response rate increased from 44% in the low-dose group to 78% in the high-dose group ( 46 ).…”

Add-On Effect of Hemagglutinating Virus of Japan Envelope Combined with Chemotherapy or Immune Checkpoint Inhibitor against Malignant Pleural Mesothelioma: An In Vivo Study

“…In this situation, we focused our attention on hemagglutinating virus of Japan envelope (HVJ-E) as a preparation that can be expected to be effective in combination with chemotherapy or ICIs to further improve treatment outcomes. HVJ-E exerts its therapeutic effect by enhancing the cancer immune cycle through activation of antigen-presenting cells such as dendritic cells and macropahges [9], killing cancer cells by cytotoxic T cells and Natural killer cells [10,11], and inducing M1-type macropahges through diverse immune activatinon effects [12][13][14]. In combination with chemotherapy and ICIs, HVJ-E is expected to have a high antitumor effect.…”