University of Siena, Siena, Italy; Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy.
Centrul de Oncologie Sf. Nectarie, Oncologie Medicala, Craiova, Romania.
ESMO Open. 2024 Mar;9(3):102387. doi: 10.1016/j.esmoop.2024.102387. Epub 2024 Feb 23.
POD1UM-203, an open-label, multicenter, phase II study, evaluated retifanlimab, a humanized monoclonal antibody targeting programmed cell death protein-1 (PD-1) in patients with selected solid tumors where immune checkpoint inhibitor therapies have previously shown efficacy.
Eligible patients (≥18 years) had measurable disease and included unresectable or metastatic melanoma, treatment-naive metastatic non-small-cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression (tumor proportion score ≥50%), cisplatin-ineligible locally advanced/metastatic urothelial carcinoma (UC) with PD-L1 expression (combined positive score ≥10%), or treatment-naive locally advanced/metastatic clear-cell renal cell carcinoma (RCC). Retifanlimab 500 mg was administered intravenously every 4 weeks as a 30-min infusion. The primary endpoint was investigator-assessed overall response rate.
Overall, 121 patients (35 melanoma, 23 NSCLC, 29 UC, 34 RCC) were enrolled and treated. The overall response rate [95% confidence interval (CI)] was 40.0% (23.9-57.9) in the melanoma cohort, 34.8% (16.4-57.3) in the NSCLC cohort, 37.9% (20.7-57.7) in the UC cohort, and 23.5% (10.7-41.2) in the RCC cohort. Median duration of response was 11.5 months (95% CI 2.2-not reached) in the UC cohort, and was not reached in the other cohorts. Retifanlimab safety was consistent with previous experience for PD-(L)1 inhibitors.
Retifanlimab demonstrated durable antitumor activity in patients with melanoma, NSCLC, UC, or RCC. The efficacy and safety of retifanlimab were as expected for a PD-(L)1 inhibitor. These data support further study of retifanlimab in solid tumors.
POD1UM-203 是一项开放标签、多中心、二期研究，评估了靶向程序性死亡蛋白-1（PD-1）的人源化单克隆抗体 retifanlimab 在先前已显示免疫检查点抑制剂治疗有效的选定实体瘤患者中的疗效。
符合条件的患者（≥18 岁）有可测量的疾病，包括不可切除或转移性黑色素瘤、初治转移性非小细胞肺癌（NSCLC）且高程序性死亡配体 1（PD-L1）表达（肿瘤比例评分≥50%）、不适合顺铂的局部晚期/转移性尿路上皮癌（UC）且 PD-L1 表达（联合阳性评分≥10%），或初治局部晚期/转移性透明细胞肾细胞癌（RCC）。Retifanlimab 500mg 作为 30 分钟输注，每 4 周静脉输注一次。主要终点为研究者评估的总缓解率。
共有 121 名患者（35 名黑色素瘤患者、23 名 NSCLC 患者、29 名 UC 患者、34 名 RCC 患者）入组并接受治疗。黑色素瘤队列的总缓解率[95%置信区间（CI）]为 40.0%（23.9-57.9），NSCLC 队列为 34.8%（16.4-57.3），UC 队列为 37.9%（20.7-57.7），RCC 队列为 23.5%（10.7-41.2）。UC 队列中反应持续时间的中位数为 11.5 个月（95%CI 2.2-未达到），其他队列中未达到。Retifanlimab 的安全性与之前 PD-（L）1 抑制剂的经验一致。
Retifanlimab 显示出在黑色素瘤、NSCLC、UC 或 RCC 患者中具有持久的抗肿瘤活性。Retifanlimab 的疗效和安全性与 PD-（L）1 抑制剂一致。这些数据支持进一步研究 retifanlimab 在实体瘤中的应用。
