PURPOSE The effectiveness of immune checkpoint inhibitors (ICI) is limited in pancreatic ductal adenocarcinoma (PDAC). We conducted a phase I study to evaluate the safety of ICI with stereotactic body radiation therapy (SBRT) in patients with metastatic PDAC. PATIENTS AND METHODS Patients enrolled must have received at least one line of prior systemic chemotherapy for metastatic disease. Cohorts A1 and A2 received durvalumab every 2 weeks plus either 8 Gy in one fraction of SBRT on day 1 or 25 Gy in five fractions on day -3 to +1. Cohorts B1 and B2 received durvalumab plus tremelimumab every 4 weeks and either 8 Gy in one fraction of SBRT on day 1 or 25 Gy in five fractions on day -3 to +1. ICIs were continued until unacceptable toxicity or disease progression. The primary objective was the safety and feasibility of treatment. Objective response was assessed in lesions not subjected to SBRT. RESULTS Fifty-nine patients were enrolled and 39 were evaluable for efficacy. No dose-limiting toxicities were seen. The most common adverse event was lymphopenia. Two patients achieved a partial response (one confirmed and the other unconfirmed). The overall response rate was 5.1%. Median PFS and OS was 1.7 months [95% confidence intervals (CI), 0.8-2.0 months] and 3.3 months (95% CI, 1.2-6.6 months) in cohort A1; 2.5 months (95% CI, 0.1-3.7 months) and 9.0 months (95% CI, 0.5-18.4 months) in A2; 0.9 months (95% CI, 0.7-2.1 months) and 2.1 months (95% CI, 1.1-4.3 months) in B1; and 2.3 months (95% CI, 1.9-3.4 months) and 4.2 months (95% CI, 2.9-9.3 months) in B2. CONCLUSIONS The combination of ICI and SBRT has an acceptable safety profile and demonstrates a modest treatment benefit in patients with metastatic PDAC.

中文翻译：

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转移性胰管腺癌患者的免疫检查点封锁与立体定向身体放疗相结合。

目的免疫检查点抑制剂（ICI）在胰腺导管腺癌（PDAC）中的有效性受到限制。我们进行了一项I期研究，以评估ICI和立体定向放射治疗（SBRT）对转移性PDAC患者的安全性。患者和方法入组患者必须接受过至少一线的先前用于转移性疾病的全身化疗。队列A1和A2每2周接受durvalumab联合治疗，在第1天的一小部分SBRT中服用8 Gy，在第3天至+1的五部分中服用25 Gy。队列B1和B2每4周接受durvalumab加tremelimumab的治疗，第1天在SBRT的一小部分中接受8 Gy的治疗，第-3天至+1接受5 Gy的25 Gy。继续进行ICI，直到出现不可接受的毒性或疾病进展。主要目标是治疗的安全性和可行性。在未接受SBRT的病变中评估了客观反应。结果共有59例患者入选，其中39例可评估疗效。未见剂量限制性毒性。最常见的不良反应是淋巴细胞减少。两名患者获得了部分缓解（一名已确认，另一名未确认）。整体回应率为5.1％。在队列A1中，PFS和OS的中位数为1.7个月[95％置信区间（CI），0.8-2.0个月]和3.3个月（95％CI，1.2-6.6个月）；A2为2.5个月（95％CI，0.1-3.7个月）和9.0个月（95％CI，0.5-18.4个月）；B1为0.9个月（95％CI，0.7-2.1个月）和2.1个月（95％CI，1.1-4.3个月）；B2分别为2.3个月（95％CI，1.9-3.4个月）和4.2个月（95％CI，2.9-9.3个月）。