背景:Penpulimab,新一代抗程序性细胞死亡-1免疫球蛋白G1单克隆抗体,被工程化以优化受体占据并消除片段可结晶γ介导的效应子功能。在这个多中心,1b/2期,多队列研究,目的是研究疗效,安全,和penpulimab在晚期实体瘤中的免疫原性。
方法:无法切除的患者,我们从6个中心纳入了晚期实体瘤,每2周第1天接受200mgpenpulimab治疗,治疗长达24个月.主要终点是实体瘤疗效评价标准的客观缓解率(ORR),版本标准1.1。
结果:在2019年9月2日至2020年1月1日之间,招募了65名患者并接受了penpulimab。在数据截止时(2022年5月11日),中位随访时间为12.6个月(范围,1.1-28.6个月)。ORR为12.3(95%置信区间[CI],5.5%-22.8%),三个(4.6%)完全响应和五个(7.7%)部分响应。12名患者(18.5%)病情稳定,导致疾病控制率为30.8%(95%CI,19.9%-43.4%)。未达到中位反应持续时间(95%CI,6.70个月至不可估计)。在所有队列中,中位无进展生存期为1.74个月(95%CI,1.41-2.69个月),中位总生存期为16.59个月(95%CI,7.82~22.18个月).3级或以上治疗相关不良事件和免疫相关不良事件分别发生在9.2%和27.7%的患者中。分别。在一名患者中观察到对penpulimab的阳性抗药物抗体反应(1.8%)。
结论:Penpulimab显示有希望的抗肿瘤活性,具有可接受的安全性,为实体瘤提供了一种潜在的新治疗方法。这些发现支持对penpulimab的持久活性和安全性的评估,作为单一疗法或联合疗法,在特定的恶性肿瘤中。
BACKGROUND: Penpulimab, a new-generation antiprogrammed cell death-1 immunoglobulin G1 monoclonal antibody, was engineered to optimize receptor occupancy and eliminate fragment crystallizable γ-mediated effector function. In this multicenter, phase 1b/2, multicohort study, the objective was to investigate the efficacy, safety, and immunogenicity of penpulimab in advanced solid tumors.
METHODS: Patients who had unresectable, advanced solid tumors were enrolled from six centers and received 200 mg penpulimab on day 1 every 2 weeks for up to 24 months. The primary end point was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors, version criteria 1.1.
RESULTS: Between September 2, 2019, and January 1, 2020, 65 patients were enrolled and received penpulimab. At the time of data cutoff (May 11, 2022), the median follow-up was 12.6 months (range, 1.1-28.6 months). The ORR was 12.3 (95% confidence interval [CI], 5.5%-22.8%), with three (4.6%) complete responses and five (7.7%) partial responses. Twelve patients (18.5%) achieved stable disease, resulting in a disease control rate of 30.8% (95% CI, 19.9%-43.4%). The median duration of response was not reached (95% CI, 6.70 months to not estimable). In all cohorts, the median progression-free survival was 1.74 months (95% CI, 1.41-2.69 months), and the median overall survival was 16.59 months (95% CI, 7.82-22.18 months). Grade 3 or greater treatment-related adverse events and immune-related adverse events occurred in 9.2% and 27.7% of patients, respectively. Positive antidrug antibody responses to penpulimab were observed in one patient (1.8%).
CONCLUSIONS: Penpulimab showed promising antitumor activity with an acceptable safety profile, offering a potential new treatment approach for solid tumors. These findings supported the evaluation of penpulimab\'s durable activity and safety, as monotherapy or in combination therapy, in specific malignancies.