BO-112联合帕博利珠单抗治疗抗PD-1耐药的晚期黑色素瘤患者：II期临床试验SPOTLIGHT-203
BO-112 Plus Pembrolizumab for Patients With Anti-PD-1-Resistant Advanced Melanoma: Phase II Clinical Trial SPOTLIGHT-203.
作者信息
Márquez-Rodas Iván, Dutriaux Caroline, Saiag Philippe, de la Cruz Merino Luis, Castañón Álvarez Eduardo, Robert Caroline, Rodríguez-Moreno Juan F, Arance Ana, Cerezuela-Fuentes Pablo, Montaudié Henri, Sanmamed Miguel F, González-Cao María, Charles Julie, López Criado María Pilar, Berrocal Alfonso, de Miguel Enrique, Funck-Brentano Elisa, Prey Sorilla, Álamo de la Gala Mᵃ Carmen, Melero Ignacio, Avilés-Izquierdo Jose Antonio, Roman Ruth, Garcia-Pelaez Beatriz, Rodriguez Sonia, Trnkova Zuzana Jirakova, Quintero Marisol, Maciá Sonia, Chaney Marya F, Dalle Stephane
机构信息
Hospital General Universitario Gregorio Marañon, Madrid, Spain.
Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
出版信息
J Clin Oncol. 2025 Sep;43(25):2806-2815. doi: 10.1200/JCO-24-02595. Epub 2025 Jun 27.
PURPOSE
Patients with anti-PD-1-resistant melanoma (MEL) have no well-defined standard of care. BO-112 is a synthetic, double-stranded RNA (poly I:C) nanoplexed with polyethylenimine that when administered intratumorally has showed in patients with solid tumors potential to revert this resistance. We report efficacy and safety of the phase II clinical trial of intratumoral BO-112 plus intravenous pembrolizumab for patients with anti-PD-1-resistant MEL (ClinicalTrials.gov identifier: NCT04570332).
METHODS
Forty-two patients were treated with intratumoral BO-112 once every week for 7 weeks and then once every 3 weeks (up to 2 mg and up to eight lesions per treatment) combined with 200 mg pembrolizumab once every 3 weeks until progressive disease, unacceptable toxicity, death, or up to 1 year. Primary end point was RECIST 1.1 objective response rate (ORR) by independent central radiology review in modified intention-to-treat population (mITT; patients evaluable for response) with 20% ORR positivity threshold. Secondary key end points were progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety.
RESULTS
For mITT, there were 40 patients and the ORR was 25%, with 10% complete, 15% partial, and 40% stable disease, with nonachieved (NA) median DOR (95% CI, 8.3 to NA). For ITT, there were 42 patients, and the median PFS and OS were 3.7 months (95% CI, 2.2 to 9.2) and NA (95% CI, 9.9 to NA), respectively, with 54% patients alive at 24 months. The combination was well tolerated: 16 patients (38.1%) experiencing ≥G3-4 adverse events, four (9.5%) drug-related, and no deaths related to treatment.
CONCLUSION
The clinical trial has met its primary end point (ORR) making BO-112 with pembrolizumab a potential strategy to revert anti-PD-1 resistance in patients with MEL. PFS results are in line with other clinical trials in anti-PD-1-resistant scenario, with promising OS data.
目的
抗程序性死亡蛋白1（PD-1）耐药的黑色素瘤（MEL）患者没有明确的标准治疗方案。BO-112是一种与聚乙烯亚胺纳米复合的合成双链RNA（聚肌胞苷酸），瘤内给药时已显示出在实体瘤患者中具有逆转这种耐药性的潜力。我们报告了瘤内注射BO-112联合静脉注射帕博利珠单抗用于抗PD-1耐药MEL患者的II期临床试验的疗效和安全性（ClinicalTrials.gov标识符：NCT04570332）。
方法
42例患者接受瘤内注射BO-112，每周1次，共7周，然后每3周1次（每次最多2mg，每次最多8个病灶），联合每3周200mg帕博利珠单抗，直至疾病进展、出现不可接受的毒性、死亡或最长1年。主要终点是经独立中心放射学评估的改良意向性治疗人群（mITT；可评估缓解情况的患者）中根据实体瘤疗效评价标准（RECIST）1.1的客观缓解率（ORR），ORR阳性阈值为20%。次要关键终点是无进展生存期（PFS）、总生存期（OS）、缓解持续时间（DOR）和安全性。
结果
对于mITT人群，有4个0例患者，ORR为25%，其中完全缓解10%，部分缓解15%，疾病稳定40%，缓解持续时间中位数未达到（NA）（95%CI，8.3至NA）。对于意向性治疗（ITT）人群，有42例患者，PFS中位数和OS中位数分别为3.7个月（95%CI，2.2至9.2）和未达到（95%CI，9.9至NA），24个月时54%的患者存活。该联合治疗耐受性良好：16例患者（38.1%）发生≥3/4级不良事件，4例（9.5%）与药物相关，无治疗相关死亡。
结论
该临床试验达到了主要终点（ORR），使BO-112联合帕博利珠单抗成为逆转MEL患者抗PD-1耐药的一种潜在策略。PFS结果与抗PD-1耐药情况下的其他临床试验一致，OS数据前景良好。
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