Abstract：
BACKGROUND: Locally advanced or metastatic squamous carcinoma of the anal canal (SCAC) has poor prognosis following platinum-based chemotherapy. Retifanlimab (INCMGA00012), a humanized monoclonal antibody targeting programmed death protein-1 (PD-1), demonstrated clinical activity across a range of solid tumors in clinical trials. We present results from POD1UM-202 (NCT03597295), an open-label, single-arm, multicenter, phase II study evaluating retifanlimab in patients with previously treated advanced or metastatic SCAC.
METHODS: Patients ≥18 years of age had measurable disease and had progressed following, or were ineligible for, platinum-based therapy. Retifanlimab 500 mg was administered intravenously every 4 weeks. The primary endpoint was overall response rate (ORR) by independent central review. Secondary endpoints were duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.
RESULTS: Overall, 94 patients were enrolled. At a median follow-up of 7.1 months (range, 0.9-19.4 months), ORR was 13.8% [95% confidence interval (CI) 7.6% to 22.5%], with one complete response (1.1%) and 12 partial responses (12.8%). Responses were observed regardless of human immunodeficiency virus or human papillomavirus status, programmed death ligand 1 (PD-L1) expression, or liver metastases. Stable disease was observed in 33 patients (35.1%) for a DCR of 48.9% (95% CI 38.5% to 59.5%). Median DOR was 9.5 months (range, 5.6 months-not estimable). Median (95% CI) PFS and OS were 2.3 (1.9-3.6) and 10.1 (7.9-not estimable) months, respectively. Retifanlimab safety in this population was consistent with previous experience for the PD-(L)1 inhibitor class.
CONCLUSIONS: Retifanlimab demonstrated clinically meaningful and durable antitumor activity, and an acceptable safety profile in patients with previously treated locally advanced or metastatic SCAC who have progressed on or are intolerant to platinum-based chemotherapy.
METHODS: Patients ≥18 years of age had measurable disease and had progressed following, or were ineligible for, platinum-based therapy. Retifanlimab 500 mg was administered intravenously every 4 weeks. The primary endpoint was overall response rate (ORR) by independent central review. Secondary endpoints were duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.
RESULTS: Overall, 94 patients were enrolled. At a median follow-up of 7.1 months (range, 0.9-19.4 months), ORR was 13.8% [95% confidence interval (CI) 7.6% to 22.5%], with one complete response (1.1%) and 12 partial responses (12.8%). Responses were observed regardless of human immunodeficiency virus or human papillomavirus status, programmed death ligand 1 (PD-L1) expression, or liver metastases. Stable disease was observed in 33 patients (35.1%) for a DCR of 48.9% (95% CI 38.5% to 59.5%). Median DOR was 9.5 months (range, 5.6 months-not estimable). Median (95% CI) PFS and OS were 2.3 (1.9-3.6) and 10.1 (7.9-not estimable) months, respectively. Retifanlimab safety in this population was consistent with previous experience for the PD-(L)1 inhibitor class.
CONCLUSIONS: Retifanlimab demonstrated clinically meaningful and durable antitumor activity, and an acceptable safety profile in patients with previously treated locally advanced or metastatic SCAC who have progressed on or are intolerant to platinum-based chemotherapy.
摘要：
背景：局部晚期或转移性肛管鳞状细胞癌（SCAC）在铂类化疗后预后不良。Retifanlimab(INCMGA00012),一种针对程序性死亡蛋白-1（PD-1）的人源化单克隆抗体，在临床试验中证明了一系列实体瘤的临床活性。我们提供了来自POD1UM-202(NCT03597295)的结果，一个开放的标签，单臂,多中心，II期研究评估retifanlimab在先前治疗过的晚期或转移性SCAC患者中的应用。
方法：年龄≥18岁的患者有可测量的疾病，或者没有资格，铂类治疗。每4周静脉内施用Retifanlimab500mg。主要终点是独立中央评估的总体缓解率（ORR）。次要终点是反应持续时间（DOR），疾病控制率（DCR），无进展生存期（PFS），总生存期（OS），和安全。
结果：总体而言，94例患者入组。中位随访7.1个月(范围，0.9-19.4个月)，ORR为13.8%[95%置信区间(CI)7.6%至22.5%]，1个完全应答(1.1%)和12个部分应答(12.8%)。无论人类免疫缺陷病毒或人乳头瘤病毒状态如何，都观察到反应。程序性死亡配体1（PD-L1）表达，或肝转移。33例患者（35.1%）病情稳定，DCR为48.9%（95%CI38.5%至59.5%）。DOR中位数为9.5个月(范围，5.6个月-不可估计)。中位数（95%CI）PFS和OS分别为2.3（1.9-3.6）和10.1（7.9-不可估计）个月，分别。此人群中的Retifanlimab安全性与PD-（L）1抑制剂类别的先前经验一致。
结论：Retifanlimab表现出临床意义和持久的抗肿瘤活性，在先前接受过局部晚期或转移性SCAC治疗的患者中，在铂类化疗中进展或不耐受，安全性可接受。
方法：年龄≥18岁的患者有可测量的疾病，或者没有资格，铂类治疗。每4周静脉内施用Retifanlimab500mg。主要终点是独立中央评估的总体缓解率（ORR）。次要终点是反应持续时间（DOR），疾病控制率（DCR），无进展生存期（PFS），总生存期（OS），和安全。
结果：总体而言，94例患者入组。中位随访7.1个月(范围，0.9-19.4个月)，ORR为13.8%[95%置信区间(CI)7.6%至22.5%]，1个完全应答(1.1%)和12个部分应答(12.8%)。无论人类免疫缺陷病毒或人乳头瘤病毒状态如何，都观察到反应。程序性死亡配体1（PD-L1）表达，或肝转移。33例患者（35.1%）病情稳定，DCR为48.9%（95%CI38.5%至59.5%）。DOR中位数为9.5个月(范围，5.6个月-不可估计)。中位数（95%CI）PFS和OS分别为2.3（1.9-3.6）和10.1（7.9-不可估计）个月，分别。此人群中的Retifanlimab安全性与PD-（L）1抑制剂类别的先前经验一致。
结论：Retifanlimab表现出临床意义和持久的抗肿瘤活性，在先前接受过局部晚期或转移性SCAC治疗的患者中，在铂类化疗中进展或不耐受，安全性可接受。
