MP0250 是一种设计的锚蛋白重复蛋白，可特异性抑制血管内皮生长因子 A (VEGF-A) 和肝细胞生长因子 (HGF)，旨在通过破坏肿瘤微环境来增强癌症治疗。 MP0250 在实体瘤患者中进行的 1 期试验令人鼓舞的结果促使对多发性骨髓瘤 (MM) 进行进一步研究，因为据报道 MP0250 的两个靶点都是 MM 发病机制的驱动因素。在这项针对蛋白酶体抑制剂和/或免疫调节药物复发或难治性 MM 患者的开放标签、单臂 1b/2 期研究 (NCT03136653) 中，每 3 周给予 MP0250 一次，并采用标准硼替佐米/地塞米松方案。 33 名患者接受了至少一剂 MP0250。最常见的治疗相关不良事件是动脉高血压（58.1%）、血小板减少症（32.3%）、蛋白尿（29.0%）和外周水肿（19.4%）。在可评估缓解的 28 名患者中（中位年龄：60 岁 [范围 44-75]），9 名患者至少达到部分缓解，相当于 32.1% 的总体缓解率（95% 置信区间 [CI]：17.9%、50.7%） ），中位缓解持续时间为 8 个月（95% CI 5-NR）。另外三名患者实现了最低反应，九名患者疾病稳定，为最佳总体反应。总体中位无进展生存期为 4.2 个月（95% CI 1.9-7.1）。这些发现与最近在可比患者队列中测试新药的试验结果一致，并为接受 MP0250 联合硼替佐米/地塞米松治疗的难治性/复发性 MM 患者提供了临床获益的初步证据。需要对新兴 MM 治疗领域进行进一步的临床评估，以确认 MP0250 的临床潜力。© 2024 Molecular Partners AG 和作者。 eJHaem 由英国血液学会和 John Wiley 出版

MP0250 is a designed ankyrin repeat protein that specifically inhibits both vascular endothelial growth factor A (VEGF-A) and hepatocyte growth factor (HGF), aiming at potentiating cancer therapy by disrupting the tumour microenvironment. Encouraging results from a phase 1 trial of MP0250 in patients with solid tumours prompted further investigation in multiple myeloma (MM) as both MP0250 targets are reported to be drivers of MM pathogenesis. In this open-label, single-arm phase 1b/2 study (NCT03136653) in patients with proteasome inhibitor- and/or immunomodulatory drug-relapsed or refractory MM, MP0250 was administered every 3 weeks with standard bortezomib/dexamethasone regimen. Thirty-three patients received at least one dose of MP0250. The most frequent treatment-related adverse events were arterial hypertension (58.1%), thrombocytopenia (32.3%), proteinuria (29.0%) and peripheral oedema (19.4%). Of the 28 patients evaluable for response (median age: 60 [range 44-75]), nine achieved at least partial response, corresponding to an overall response rate of 32.1% (95% confidence interval [CI]: 17.9%, 50.7%), with a median duration of response of 8 months (95% CI 5-NR). An additional three patients achieved minimal response and nine stable diseases as the best overall response. Overall median progression-free survival was 4.2 months (95% CI 1.9-7.1). These findings are in line with the results of recent trials testing new agents on comparable patient cohorts and provide initial evidence of clinical benefit for patients with refractory/relapsed MM treated with MP0250 in combination with bortezomib/dexamethasone. Further clinical evaluation in the emerging MM treatment landscape would be required to confirm the clinical potential of MP0250.© 2024 Molecular Partners AG, and The Author(s). eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.