Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
School of Pharmacy, Southwest Medical University, Luzhou, China.
BMC Cancer. 2020 Jul 9;20(1):636. doi: 10.1186/s12885-020-07126-3.
Pancreatic 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.
This 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/m and nab-paclitaxel 125 mg/m on 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.
This 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 registration: ChiCTR ( ChiCTR2000032293 ). Registered 25 April 2020 - Retrospectively registered.
胰腺导管腺癌（PDAC）是一种致命疾病，对免疫检查点抑制剂（ICIs）的单一使用反应不佳。ICI 联合系统治疗已在各种实体瘤中显示出疗效和安全性。白蛋白紫杉醇联合吉西他滨（AG）作为晚期 PDAC 的标准一线治疗，近年来已广泛应用。ICI 和 AG 化疗联合似乎是治疗 PDAC 的一种有前途的选择。
这是一项开放标签、单臂、单中心 Ib/II 期研究。入组患者为未经系统治疗的不可切除（局部晚期或转移性）PDAC 患者。所有患者在第 1 天和第 8 天接受静脉注射吉西他滨 1000mg/m 和白蛋白紫杉醇 125mg/m，以及第 1 天每 3 周 1 次静脉注射替雷利珠单抗 240mg。患者可能因疾病进展（PD）、无法耐受的毒性、患者或研究者的要求而停止治疗。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可能性。该试验的主要目的是评估该联合治疗的安全性和总生存期（OS）；次要目的是评估客观缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）以及接受替雷利珠单抗加 AG 治疗后的切除率或 R0 切除率。此外，我们期望确定预测生物标志物（如 MMR 蛋白和 PD-L1 表达、TIL 数量、EBV 小 RNA 等），并探索这些生物标志物与肿瘤对该联合方案反应之间的相关性。
本试验是首次评估替雷利珠单抗联合 AG 化疗作为不可切除 PDAC 患者一线治疗的疗效和安全性的尝试。该 Ib/II 期研究的结果将为进一步评估不可切除 PDAC 患者的这种联合治疗方案提供初步证据。
临床试验注册：ChiCTR（ChiCTR2000032293）。注册日期：2020 年 4 月 25 日-回顾性注册。
