Study protocol for an open-label, single-arm, phase Ib/II study of combination of toripalimab, nab-paclitaxel, and gemcitabine as the first-line treatment for patients with unresectable pancreatic ductal adenocarcinoma
Study protocol for an open-label, single-arm, phase Ib/II study of combination of toripalimab, nab-paclitaxel, and gemcitabine as the first-line treatment for patients with unresectable pancreatic ductal adenocarcinoma
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特瑞普利单抗、白蛋白结合型紫杉醇和吉西他滨组合作为不可切除的胰腺导管腺癌患者一线治疗的开放标签、单臂、Ib/II 期研究的研究方案
DOI：
10.1186/s12885-020-07126-3
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发表时间：
2020-07-09
期刊：
影响因子：
3.8
通讯作者：
Cao, Dan
中科院分区：
文献类型：
--
作者：
Shui, Lin;Cheng, Ke;Cao, Dan
背景胰腺导管腺癌（PDAC）是一种致命性疾病，对单次使用免疫检查点抑制剂（ICIs）反应不佳。 ICI 与全身治疗相结合已在多种实体瘤中显示出有效性和安全性。白蛋白结合型紫杉醇和吉西他滨（AG）作为晚期PDAC的标准一线治疗方法，近年来得到广泛应用。 ICI 和 AG 化疗的组合似乎是治疗 PDAC 的一个有前途的选择。方法这是一项开放标签、单臂、单中心 Ib/II 期试验。入组受试者为既往未接受全身治疗的不可切除（局部晚期或转移性）PDAC 患者。所有受试者在第 1 天和第 8 天接受静脉注射吉西他滨 1000 mg/m2 和白蛋白结合型紫杉醇 125 mg/m2，并在第 1 天每 3 周静脉注射 240 mg 特瑞普利单抗。由于疾病进展（PD）、无法耐受的毒性、患者或研究人员的要求，受试者可能会停止治疗。对于评估为部分缓解（PR）的局部晚期患者，外科医生需要评估手术的可能性。该试验的主要目的是评估该联合疗法的安全性和总生存期（OS）；次要目标涉及特瑞普利单抗联合AG治疗后客观缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）以及切除率或R0切除率的评估。此外，我们期望鉴定预测性生物标志物（如MMR蛋白和PD-L1表达、TILs数量、EBV小RNA等），并探讨这些生物标志物与肿瘤对该联合方案的反应之间的相关性。讨论本试验是首次尝试评估特瑞普利单抗联合AG化疗作为不可切除PDAC患者一线治疗的有效性和安全性。这项Ib/II期研究的结果将为进一步评估这种联合治疗方案治疗不可切除的PDAC患者提供初步证据。 试验注册试验注册：ChiCTR（ChiCTR2000032293）。 2020 年 4 月 25 日注册 - 追溯注册。
BackgroundPancreatic ductal adenocarcinoma (PDAC) is a fatal disease with a dismal response to single-use of immune checkpoint inhibitors (ICIs). ICIs combined with systemic therapy has shown efficacy and safety in various solid tumors. Nab-paclitaxel and gemcitabine (AG), as the standard first-line treatment for advanced PDAC, has been widely used in recent years. The combination of ICIs and AG chemotherapy appears to be a promising option in the treatment of PDAC.MethodsThis is an open-label, single-arm, and single-center phase Ib/II trial. The enrolled subjects are the unresectable (locally advanced or metastatic) PDAC patients without previous systemic treatments. All subjects receive an intravenous injection of gemcitabine 1000 mg/m2and nab-paclitaxel 125 mg/m2on day 1 and day 8, along with toripalimab 240 mg at day 1 every 3 weeks. The subjects may discontinue the treatment because of progression disease (PD), intolerable toxicities, requirements of patients or researchers. For local advanced patients who are evaluated as partial response (PR), surgeons need to assess the surgical possibility. The primary objective of this trial is to evaluate the safety and overall survival (OS) of this combination therapy; and the secondary objective is related to the assessment of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and the rate of resection or R0 resection after receiving toripalimab plus AG treatment. Besides, we expect to identify the predictive biomarkers (such as MMR protein and PD-L1 expression, the number of TILs, the small RNA of EBV and so on) and explore the correlation between these biomarkers and tumor response to this combined regimen.DiscussionThis trial is the first attempt to evaluate the efficacy and safety of the combination of toripalimab plus AG chemotherapy as a first-line treatment for unresectable PDAC patients. The results of this phase Ib/II study will provide preliminary evidence for further assessment of this combined therapeutic regimen for unresectable PDAC patients.Trial registrationTrial registration: ChiCTR ( ChiCTR2000032293 ). Registered 25 April 2020 - Retrospectively registered.