■BVAC-C,在一项I期研究中,用重组HPVE6/E7转染的基于B细胞和单核细胞的免疫治疗疫苗在HPV阳性复发性宫颈癌患者中具有良好的耐受性.这项IIa期研究调查了BVAC-C在HPV16或18阳性宫颈癌患者中的抗肿瘤活性,这些患者在铂类联合化疗后复发。
■患者分为3组;第1组,0、4、8周注射BVAC-C;第2组,0、4、8、12周注射BVAC-C;第3组,0、4、8、12周注射BVAC-C,第2、6、10、14周注射拓扑替康。主要终点是由独立放射科医师根据实体瘤版本1.1中的反应评估标准评估的安全性和客观反应率(ORR)。次要终点包括疾病控制率(DCR),响应持续时间(DOR),无进展生存期(PFS),总生存率(OS)。
■在可用于分析的30名患者中,ORR为19.2%(第1组:20.0%(3/15),手臂2:33.3%(2/6),Arm3:0%),DCR为53.8%(第1组:57.1%,第2臂:28.6%,Arm3:14.3%)。平均DOR为7.5个月(95%CI7.1-未报告),中位PFS为5.8个月(95%CI4.2-10.3),中位OS为17.7个月(95%CI12.0-未报告)。所有评估的患者在接种疫苗时不仅显示出炎性细胞因子应答(IFN-γ或TNF-α),而且显示出有效的E6/E7特异性T细胞应答。疫苗接种后患者的免疫反应与其临床反应相关。
■BVAC-C代表了该患者群体的二线治疗方案和可管理的安全性。需要进一步的研究来确定潜在的反应生物标志物。
■ClinicalTrials.gov,标识符NCT02866006。
BVAC-C, a B cell- and monocyte-based immunotherapeutic vaccine transfected with recombinant HPV E6/E7, was well tolerated in HPV-positive recurrent cervical carcinoma patients in a phase I study. This phase IIa study investigates the antitumor activity of BVAC-C in patients with HPV 16- or 18-positive cervical cancer who had experienced recurrence after a platinum-based combination chemotherapy.
Patients were allocated to 3 arms; Arm 1, BVAC-C injection at 0, 4, 8 weeks; Arm 2, BVAC-C injection at 0, 4, 8, 12 weeks; Arm 3, BVAC-C injection at 0, 4, 8, 12 weeks with topotecan at 2, 6, 10, 14 weeks. Primary endpoints were safety and objective response rate (ORR) as assessed by an independent radiologist according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included the disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).
Of the 30 patients available for analysis, the ORR was 19.2% (Arm 1: 20.0% (3/15), Arm 2: 33.3% (2/6), Arm3: 0%) and the DCR was 53.8% (Arm 1: 57.1%, Arm 2: 28.6%, Arm3: 14.3%). The median DOR was 7.5 months (95% CI 7.1-not reported), the median PFS was 5.8 months (95% CI 4.2-10.3), and the median OS was 17.7 months (95% CI 12.0-not reported). All evaluated patients showed not only inflammatory cytokine responses (IFN-γ or TNF-α) but also potent E6/E7-specific T cell responses upon vaccinations. Immune responses of patients after vaccination were correlated with their clinical responses.
BVAC-C represents a promising treatment option and a manageable safety profile in the second-line setting for this patient population. Further studies are needed to identify potential biomarkers of response.
ClinicalTrials.gov, identifier NCT02866006.