Grignani Giovanni, Rutkowski Piotr, Lebbé Céleste, Guida Michele, Gaudy-Marqueste Caroline, Spagnolo Francesco, Burgess Melissa, Morano Federica, Montaudié Henri, Depenni Roberta, Spada Francesca, Yeung Cecilia C S, Pulini Jennifer, Cornfeld Mark, Tian Chuan, Bhatia Shailender
Department of Oncology, Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Italy
Department of Soft Tissue/Bone Sarcoma and Melanoma, The Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Warsaw, Poland.
J Immunother Cancer. 2025 Aug 11;13(8):e012478. doi: 10.1136/jitc-2025-012478.
POD1UM-201, an open-label, single-arm, phase II multiregional study, evaluated efficacy and tolerability of retifanlimab, a humanized monoclonal antibody targeting programmed cell death protein-1 (PD-1) in chemotherapy-naive patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).
Patients were enrolled across 34 sites in the USA, Canada, and Europe. Eligible patients were ≥18 years with confirmed recurrent advanced locoregional or metastatic MCC not amenable to surgery or radiation therapy, had not received previous systemic treatment, had measurable disease, and Eastern Cooperative Oncology Group performance status 0-1. Retifanlimab 500 mg was administered intravenously every 4 weeks (Q4W) for up to 2 years. The primary endpoint was objective response rate (ORR). Key secondary endpoints included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.
A total of 101 patients were enrolled between February 12, 2019, and June 16, 2021, with a median duration of follow-up for response of 22.2 (range: 1.1-55.3) months. ORR was 54.5% (95% CI: 44.2% to 64.4%; n=55), including 18 patients (17.8%) with complete responses (CRs) and 37 (36.6%) with partial responses (PRs). DCR was 60.4% (95% CI: 50.2% to 70.0%; n=61). Median DOR was not reached (95% CI: 14.0 months to not estimable (NE)) in patients who achieved CR and was 25.3 months (95% CI: 14.2 months to NE) in those with PR. With a median follow-up of 9.3 (range: 0.0-57.1) months, the estimated median PFS was 16.0 months (95% CI: 9.0 months to 32.2). Median OS was not reached with 63% of patients alive at 3 years. The safety profile was representative of the PD-(ligand)1 inhibitor class, with grade 3 immune-related adverse events occurring in 11 patients (10.9%).
Retifanlimab 500 mg Q4W led to frequent and durable responses in chemotherapy-naive patients with advanced MCC with an acceptable safety profile. Retifanlimab represents a new immunotherapy option for patients with locally advanced or metastatic MCC.
NCT03599713; EudraCT 2018-001627-39.
POD1UM - 201是一项开放标签、单臂、II期多区域研究，评估了瑞替凡利单抗（一种靶向程序性细胞死亡蛋白1（PD - 1）的人源化单克隆抗体）在未经化疗的复发性局部晚期或转移性默克尔细胞癌（MCC）患者中的疗效和耐受性。
患者在美国、加拿大和欧洲的34个地点入组。符合条件的患者年龄≥18岁，确诊为复发性晚期局部区域或转移性MCC，不适合手术或放射治疗，未接受过先前的全身治疗，有可测量的疾病，且东部肿瘤协作组体能状态为0 - 1。每4周（Q4W）静脉注射瑞替凡利单抗500mg，最长持续2年。主要终点是客观缓解率（ORR）。关键次要终点包括缓解持续时间（DOR）、疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）和安全性。
2019年2月12日至2021年6月16日期间共入组101例患者，缓解的中位随访时间为22.2（范围：1.1 - 55.3）个月。ORR为54.5%（95%CI：44.2%至64.4%；n = 55），包括18例（17.8%）完全缓解（CR）患者和37例（36.6%）部分缓解（PR）患者。DCR为60.4%（95%CI：50.2%至70.0%；n = 61）。达到CR的患者中位DOR未达到（95%CI：14.0个月至不可估计（NE）），PR患者的中位DOR为25.3个月（95%CI：14.2个月至NE）。中位随访9.3（范围：0.0 - 57.1）个月时，估计中位PFS为16.0个月（95%CI：9.0个月至32.2）。3年时63%的患者存活，中位OS未达到。安全性特征代表了PD - （配体）1抑制剂类别，11例患者（10.9%）发生3级免疫相关不良事件。
每4周一次静脉注射500mg瑞替凡利单抗可使未经化疗的晚期MCC患者频繁且持久地缓解，安全性可接受。瑞替凡利单抗是局部晚期或转移性MCC患者的一种新的免疫治疗选择。
NCT03599713；EudraCT 2018 - 001627 - 39。
