Abstract：
OBJECTIVE: In patients with epithelial ovarian cancer (EOC), the clinical efficacy of monotherapy with immune checkpoint inhibitors (ICIs) against PD-1/PD-L1 is modest. To enhance response rates to these immunotherapeutic agents and broaden the indications for their use, new approaches involving combinational therapy are needed. The immune regulator CD73 is a potential target, as it promotes tumor escape by producing immunosuppressive extracellular adenosine in the tumor microenvironment. Here, we present the results from the NSGO-OV-UMB1/ENGOT-OV-30 trial evaluating the activity of combining the anti-CD73 antibody oleclumab with the anti-PD-L1 checkpoint inhibitor durvalumab in patients with recurrent EOC.
METHODS: In this phase II open-label non-randomized study, patients with CD73-positive relapsed EOC were intravenously administered oleclumab (3000 mg, Q2W) and durvalumab (1500 mg, Q4W). The primary endpoint was disease control rate (DCR) at 16 weeks. The expression of PD-L1 and CD8 was assessed by immunohistochemistry of archival tumors.
RESULTS: This trial included 25 patients with a median age of 66 years (47-77 years). Twenty-two patients were evaluable for treatment activity analysis. The DCR was 27%, the median progression-free survival was 2.7 months (95% CI: 2.2-4.2) and the median overall survival was 8.4 months (95% CI: 5.0-13.4). Infiltration of CD8+ cells and PD-L1 expression on tumor cells were observed in partially overlapping sets of 74% of the tumor samples. Neither CD8- nor PD-L1-positivity were significantly associated with better DCR.
CONCLUSIONS: Combined treatment with oleclumab and durvalumab was safe and demonstrated limited anti-tumor activity in patients with recurrent EOC.
METHODS: In this phase II open-label non-randomized study, patients with CD73-positive relapsed EOC were intravenously administered oleclumab (3000 mg, Q2W) and durvalumab (1500 mg, Q4W). The primary endpoint was disease control rate (DCR) at 16 weeks. The expression of PD-L1 and CD8 was assessed by immunohistochemistry of archival tumors.
RESULTS: This trial included 25 patients with a median age of 66 years (47-77 years). Twenty-two patients were evaluable for treatment activity analysis. The DCR was 27%, the median progression-free survival was 2.7 months (95% CI: 2.2-4.2) and the median overall survival was 8.4 months (95% CI: 5.0-13.4). Infiltration of CD8+ cells and PD-L1 expression on tumor cells were observed in partially overlapping sets of 74% of the tumor samples. Neither CD8- nor PD-L1-positivity were significantly associated with better DCR.
CONCLUSIONS: Combined treatment with oleclumab and durvalumab was safe and demonstrated limited anti-tumor activity in patients with recurrent EOC.
摘要：
目的：在上皮性卵巢癌（EOC）患者中，免疫检查点抑制剂(ICIs)单药治疗PD-1/PD-L1的临床疗效不明显.为了提高对这些免疫治疗剂的反应率并扩大其使用的适应症，需要涉及组合治疗的新方法。免疫调节因子CD73是一个潜在的靶点，因为它通过在肿瘤微环境中产生免疫抑制性胞外腺苷来促进肿瘤逃逸。这里,我们介绍了NSGO-OV-UMB1/ENGOT-OV-30试验的结果,该试验评估了抗CD73抗体抗体与抗PD-L1检查点抑制剂durvalumab联合治疗复发性EOC患者的活性.
方法：在这项II期开放标签非随机研究中，CD73阳性复发的EOC患者静脉内给药Olumimab（3000mg，Q2W）和durvalumab（1500mg，Q4W）。主要终点是16周时的疾病控制率（DCR）。通过档案肿瘤的免疫组织化学评估PD-L1和CD8的表达。
结果：本试验纳入25名患者，中位年龄为66岁（47-77岁）。22例患者可进行治疗活动分析。DCR为27%,中位无进展生存期为2.7个月(95%CI:2.2~4.2),中位总生存期为8.4个月(95%CI:5.0~13.4).在74%的肿瘤样品的部分重叠组中观察到CD8+细胞的浸润和肿瘤细胞上的PD-L1表达。CD8和PD-L1阳性与更好的DCR均无显著相关。
结论：在复发性EOC患者中，与奥尔鲁单抗和durvalumab联合治疗是安全的，并且显示出有限的抗肿瘤活性。
方法：在这项II期开放标签非随机研究中，CD73阳性复发的EOC患者静脉内给药Olumimab（3000mg，Q2W）和durvalumab（1500mg，Q4W）。主要终点是16周时的疾病控制率（DCR）。通过档案肿瘤的免疫组织化学评估PD-L1和CD8的表达。
结果：本试验纳入25名患者，中位年龄为66岁（47-77岁）。22例患者可进行治疗活动分析。DCR为27%,中位无进展生存期为2.7个月(95%CI:2.2~4.2),中位总生存期为8.4个月(95%CI:5.0~13.4).在74%的肿瘤样品的部分重叠组中观察到CD8+细胞的浸润和肿瘤细胞上的PD-L1表达。CD8和PD-L1阳性与更好的DCR均无显著相关。
结论：在复发性EOC患者中，与奥尔鲁单抗和durvalumab联合治疗是安全的，并且显示出有限的抗肿瘤活性。
