■铂耐药或铂难治性卵巢癌(PRROC)患者的治疗选择有限,代表了相当大的未满足的医疗需求。
■评估PRROC患者腹膜内(IP)奥维莫洛基因纳米替韦克(Olvi-Vec)病毒疗法和铂类化疗联合或不联合贝伐单抗的抗肿瘤活性和安全性。
■这个开放标签,2016年9月至2019年9月,非随机多中心2期VIRO-15临床试验纳入了PRROC患者,这些患者在接受最后一次治疗后出现疾病进展.数据截止日期为2022年3月31日,数据在2022年4月至2022年9月之间进行了分析。
■通过临时IP透析导管给予Olvi-Vec,连续2次每日剂量(3×109pfu/d),然后进行含或不含贝伐单抗的铂双峰化疗。
■主要结果是通过实体瘤的反应评估标准的客观反应率(ORR),版本1.1(RECIST1.1)和癌症抗原125(CA-125)测定,无进展生存期(PFS)。次要结果包括反应持续时间(DOR),疾病控制率(DCR),安全,总生存率(OS)。
■纳入27例铂耐药(n=14)或铂难治(n=13)卵巢癌患者。中位(范围)年龄为62(35-78)岁。先前治疗线的中值(范围)为4(2-9)。所有患者均完成了Olvi-Vec输注和化疗。中位随访时间为47.0个月(95%CI,NA为35.9个月)。总的来说,按RECIST1.1计算的ORR为54%(95%CI,33%-74%),DOR为7.6个月(95%CI,3.7-9.6个月)。DCR为88%(21/24)。CA-125的ORR为85%(95%CI,65%-96%)。按RECIST1.1计算的平均PFS为11.0个月(95%CI,6.7-13.0个月),6个月的PFS率为77%。铂耐药组的PFS中位数为10.0个月(95%CI,6.4-NA月),铂难治组为11.4个月(95%CI,4.3-13.2个月)。所有患者的中位OS为15.7个月(95%CI,12.3-23.8个月),铂耐药组的中位OS为18.5个月(95%CI,11.3-23.8个月),铂难治组的中位OS为14.7个月(95%CI,10.8-33.6个月).最常见的治疗相关不良事件(TRAEs)(任何级别,3级)发热(63.0%,3.7%,分别)和腹痛(51.9%,7.4%,分别)。没有四级TRAE,没有治疗相关的停药或死亡。
■在这项2期非随机临床试验中,在PRROC患者中,Olvi-Vec以及含或不含贝伐单抗的铂类化疗作为免疫化学疗法证明了有希望的ORR和PFS,具有可控的安全性。这些产生假设的结果值得在验证性3期试验中进一步评估。
■ClinicalTrials.gov标识符:NCT02759588。
Patients with platinum-resistant or platinum-refractory ovarian cancer (PRROC) have limited therapeutic options, representing a considerable unmet medical need.
To assess antitumor activity and safety of intraperitoneal (IP) olvimulogene nanivacirepvec (Olvi-Vec) virotherapy and platinum-based chemotherapy with or without bevacizumab in patients with PRROC.
This open-label, nonrandomized multisite phase 2 VIRO-15 clinical
trial enrolled patients with PRROC with disease progression following their last prior line of therapy from September 2016 to September 2019. Data cutoff was on March 31, 2022, and data were analyzed between April 2022 and September 2022.
Olvi-Vec was administered via a temporary IP dialysis catheter as 2 consecutive daily doses (3 × 109 pfu/d) followed by platinum-doublet chemotherapy with or without bevacizumab.
Primary outcomes were objective response rate (ORR) via Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) and cancer antigen 125 (CA-125) assay, and progression-free survival (PFS). Secondary outcomes included duration of response (DOR), disease control rate (DCR), safety, and overall survival (OS).
Twenty-seven heavily pretreated patients with platinum-resistant (n = 14) or platinum-refractory (n = 13) ovarian cancer were enrolled. The median (range) age was 62 (35-78) years. The median (range) prior lines of therapy were 4 (2-9). All patients completed both Olvi-Vec infusions and chemotherapy. Median follow-up duration was 47.0 months (95% CI, 35.9 months to NA). Overall, ORR by RECIST 1.1 was 54% (95% CI, 33%-74%), with a DOR of 7.6 months (95% CI, 3.7-9.6 months). The DCR was 88% (21/24). The ORR by CA-125 was 85% (95% CI, 65%-96%). Median PFS by RECIST 1.1 was 11.0 months (95% CI, 6.7-13.0 months), and the PFS 6-month rate was 77%. Median PFS was 10.0 months (95% CI, 6.4-NA months) in the platinum-resistant group and 11.4 months (95% CI, 4.3-13.2 months) in the platinum-refractory group. The median OS was 15.7 months (95% CI, 12.3-23.8 months) in all patients, with a median OS of 18.5 months (95% CI, 11.3-23.8 months) in the platinum-resistant group and 14.7 months (95% CI, 10.8-33.6 months) in the platinum-refractory group. Most frequent treatment-related adverse events (TRAEs) (any grade, grade 3) were pyrexia (63.0%, 3.7%, respectively) and abdominal pain (51.9%, 7.4%, respectively). There were no grade 4 TRAEs, and no treatment-related discontinuations or deaths.
In this phase 2 nonrandomized clinical
trial, Olvi-Vec followed by platinum-based chemotherapy with or without bevacizumab as immunochemotherapy demonstrated promising ORR and PFS with a manageable safety profile in patients with PRROC. These hypothesis-generating results warrant further evaluation in a confirmatory phase 3
trial.
ClinicalTrials.gov Identifier: NCT02759588.