Stefan Knop, Monika Szarejko, Norbert Grząśko, Sara Bringhen, Karolin Trautmann-Grill, Artur Jurczyszyn, Angelo Vacca, Cyrus Khandanpour, Barbara Gamberi, Ludek Pour, Katrine F. Iversen, Michael T. Stumpp, Cosima Suter, Keith M. Dawson, Christof Zitt, Philippe Legenne, Vaia Stavropoulou, Martin F. Fey, Nicolas Leupin, Hartmut Goldschmidt
{"title":"一项 1b/2 期研究，评估 MP0250（一种同时靶向血管内皮生长因子 (VEGF) 和肝细胞生长因子 (HGF) 的设计霉素重复蛋白 (DARPin)）与硼替佐米和地塞米松联合治疗复发或难治性多发性骨髓瘤患者的疗效和安全性","authors":"Stefan Knop, Monika Szarejko, Norbert Grząśko, Sara Bringhen, Karolin Trautmann-Grill, Artur Jurczyszyn, Angelo Vacca, Cyrus Khandanpour, Barbara Gamberi, Ludek Pour, Katrine F. Iversen, Michael T. Stumpp, Cosima Suter, Keith M. Dawson, Christof Zitt, Philippe Legenne, Vaia Stavropoulou, Martin F. Fey, Nicolas Leupin, Hartmut Goldschmidt","doi":"10.1002/jha2.968","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <p>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).</p>\n </section>\n \n <section>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"940-950"},"PeriodicalIF":0.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.968","citationCount":"0","resultStr":"{\"title\":\"A phase 1b/2 study evaluating efficacy and safety of MP0250, a designed ankyrin repeat protein (DARPin) simultaneously targeting vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), in combination with bortezomib and dexamethasone, in patients with relapsed or refractory multiple myeloma\",\"authors\":\"Stefan Knop, Monika Szarejko, Norbert Grząśko, Sara Bringhen, Karolin Trautmann-Grill, Artur Jurczyszyn, Angelo Vacca, Cyrus Khandanpour, Barbara Gamberi, Ludek Pour, Katrine F. Iversen, Michael T. Stumpp, Cosima Suter, Keith M. Dawson, Christof Zitt, Philippe Legenne, Vaia Stavropoulou, Martin F. Fey, Nicolas Leupin, Hartmut Goldschmidt\",\"doi\":\"10.1002/jha2.968\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <p>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).</p>\\n </section>\\n \\n <section>\\n \\n <p>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. 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引用次数: 0
摘要
MP0250是一种经过设计的ankyrin重复蛋白，能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效果。MP0250在实体瘤患者中的1期试验结果令人鼓舞，这促使人们进一步研究MP0250在多发性骨髓瘤（MM）中的作用，因为据报道MP0250的两个靶点都是MM发病机制的驱动因素。 在这项开放标签、单臂1b/2期研究（NCT03136653）中，蛋白酶体抑制剂和/或免疫调节药物复发或难治性MM患者每3周接受一次MP0250治疗，同时采用标准的硼替佐米/地塞米松治疗方案。 33名患者至少接受了一次MP0250治疗。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（32.3%）、蛋白尿（29.0%）和外周水肿（19.4%）。在28名可评估应答的患者中（中位年龄：60岁[44-75岁]），9名患者至少获得了部分应答，总应答率为32.1%（95%置信区间[CI]：17.9%，50.7%），中位应答持续时间为8个月（95%置信区间：5-NR）。另有三名患者获得了最小应答，九名患者病情稳定，获得最佳总体应答。总体无进展生存期中位数为 4.2 个月（95% CI 1.9-7.1）。 这些结果与最近在可比患者群中测试新药的试验结果一致，并初步证明了MP0250联合硼替佐米/地塞米松治疗难治性/复发性MM患者的临床获益。要确认MP0250的临床潜力，还需要在新兴的MM治疗领域开展进一步的临床评估。
A phase 1b/2 study evaluating efficacy and safety of MP0250, a designed ankyrin repeat protein (DARPin) simultaneously targeting vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), in combination with bortezomib and dexamethasone, in patients with relapsed or refractory multiple myeloma
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.
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