Abstract
BVAC-C is a B cell-based and monocyte-based immuno-therapeutic vaccine transfected with a recombinant human papillomavirus (HPV) 16/18 E6/E7 gene and loaded with alpha-galactosyl ceramide, which is a natural killer T cell ligand. This phase I study sought to determine the tolerability and immunogenicity of BVAC-C in platinum-resistant recurrent cervical cancer patients. Patients with HPV 16-positive or 18-positive recurrent or persistent cervical cancer who had received at least one prior platinum-based combination chemotherapy were enrolled. BVAC-C was injected intravenously three times every four weeks, and dose escalation was planned in a three-patient cohort design at doses of 1 × 107, 4 × 107, or 1 × 108 cells/dose. Eleven patients were enrolled, and six (55%) patients had received two or more lines of platinum-based chemotherapy prior to enrollment. Treatment-related adverse events (TRAEs) were observed in 21 cycles. Most TRAEs were mild fever (n = 6.55%) or myalgia (n = 4.36%). No dose-limiting toxicities occurred. The overall response rate was 11% among nine patients evaluable, and the duration of response was 10 months. Five patients (56%) achieved a stable disease for 4.2–11 months as their best overall response. The median progression-free survival in all patients was 6.8 months (95% CI, 3.2 to infinite months), and the overall survival rate at 6 and 12 months was 89% (95% CI, 71 to 100%) and 65% (95% CI, 39 to 100%), respectively. BVAC-C induced the activation of natural killer T cells, natural killer cells, and HPV 16/18 E6/E7-specific T cells upon vaccination in all patients evaluated. BVAC-C was well tolerated and demonstrated a durable anti-tumor activity with an immune response in HPV 16-positive or 18-positive recurrent cervical carcinoma patients. A Phase 2 efficacy trial is currently underway.
Highlights
Screening programs and prophylactic vaccines have dramatically reduced the incidence of cervical cancer, treatment options for patients with metastatic or recurrent disease are very limited [1,2]
We report the results of an open-label, dose-escalation, multiple dosing phase I study to evaluate the safety, tolerability, immune response, and preliminary efficacy of based vaccine (BVAC)-C in patients with metastatic or recurrent human papillomavirus (HPV) type 16-positive or 18-positive cervical cancer after the failure of standard platinum-based chemotherapy
All patients presented with metastatic disease, which was most frequently located in the lung (n = 6.55%), lymph nodes (n = 5.45%), pelvis (n = 4.36%), and/or liver (n = 2.18%), and six patients (55%) had metastatic disease at multiple sites
Summary
Screening programs and prophylactic vaccines have dramatically reduced the incidence of cervical cancer, treatment options for patients with metastatic or recurrent disease are very limited [1,2]. Cancer cells resist the action of T cells and natural killer cells by inducing an exhaustion of those effector cells in the tumor microenvironment This can be counteracted by the BVAC-C vaccination, which activates NKT cells in the tumor microenvironment to release cytokines such as IL-21, IL-2, and IFN-γ. In this case, we report the results of an open-label, dose-escalation, multiple dosing phase I study to evaluate the safety, tolerability, immune response, and preliminary efficacy of BVAC-C in patients with metastatic or recurrent HPV type 16-positive or 18-positive cervical cancer after the failure of standard platinum-based chemotherapy
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