评估将 ofranergene obadenovec（ofra-vec，VB-111）（一种新型的基于基因的抗癌靶向疗法）添加到每周一次的紫杉醇治疗复发性铂耐药性卵巢癌 (PROC) 患者中。这种安慰剂对照、双倍治疗- 盲法 III 期试验（ClinicalTrials.gov 标识符：NCT03398655）随机分配 PROC 1:1 的患者每 8 周接受静脉注射 ofra-vec 并每周静脉注射一次紫杉醇或安慰剂加紫杉醇直至疾病进展。双重主要终点是通过盲法独立中央审查评估的总生存期（OS）和无进展生存期（PFS）。2017年12月至2022年3月期间，409名患者被随机分配。 ofra-vec 组的中位 PFS 为 5.29 个月，对照组为 5.36 个月，风险比 (HR) 1.03（CI，0.83 至 1.29；P = .7823）。 ofra-vec 的中位 OS 为 13.37 个月 vs 13.14 个月，HR 0.97（CI，0.75 至 1.27；P = .8440）。根据 RECIST 1.1 的客观缓解率 (ORR) 在两组中相似：ofra-vec 组为 28.9%，对照组为 29.6%。在两个治疗组中，对 CA-125 的反应是 PFS 和 OS 的重要预后因素。在 ofra-vec 组中，CA-125 应答者与无应答者相比，PFS 的 HR 为 0.2428（CI，0.1642 至 0.3588），OS 的 HR 为 0.3343（CI，0.2134 至 0.5238）。安全性特征是常见的短暂性流感样症状，例如发烧和寒战。在紫杉醇中添加 ofra-vec 并没有改善 PFS 或 OS。对照组的 PFS 和 ORR 超出了 AURELIA 化疗对照组的预期结果。 CA-125 反应是紫杉醇治疗的 PROC 患者 PFS 和 OS 的重要预后生物标志物。

To evaluate the addition of ofranergene obadenovec (ofra-vec, VB-111), a novel gene-based anticancer targeted therapy, to once a week paclitaxel in patients with recurrent platinum-resistant ovarian cancer (PROC).This placebo-controlled, double-blind, phase III trial (ClinicalTrials.gov identifier: NCT03398655) randomly assigned patients with PROC 1:1 to receive intravenous ofra-vec every 8 weeks with once a week IV paclitaxel or placebo with paclitaxel until disease progression. The dual primary end points were overall survival (OS) and progression-free survival (PFS) as assessed by Blinded Independent Central Review.Between December 2017 and March 2022, 409 patients were randomly assigned. The median PFS was 5.29 months in the ofra-vec arm and 5.36 months in the control arm, hazard ratio (HR) 1.03 (CI, 0.83 to 1.29; P = .7823). The median OS with ofra-vec was 13.37 months versus 13.14 months, HR 0.97 (CI, 0.75 to 1.27; P = .8440). Objective response rates (ORRs) per RECIST 1.1 were similar in both arms: 28.9% with ofra-vec versus 29.6% with control. In both treatment arms, response to CA-125 was a substantial prognostic factor for both PFS and OS. In the ofra-vec arm, the HR in CA-125 responders compared with that in nonresponders for PFS was 0.2428 (CI, 0.1642 to 0.3588), and for OS, the HR was 0.3343 (CI, 0.2134 to 0.5238). Safety profile was characterized by common transient flu-like symptoms such as fever and chills.The addition of ofra-vec to paclitaxel did not improve PFS or OS. The PFS and ORR in the control arm exceeded the results that were anticipated on the basis of the AURELIA chemotherapy control arm. CA-125 response was a substantial prognostic biomarker for PFS and OS in patients with PROC treated with paclitaxel.