Randomized phase II study of bevacizumab with weekly anetumab ravtansine or weekly paclitaxel in platinum-resistant/refractory high grade ovarian cancer (NCI trial).

IF 10 1区医学 Q1 ONCOLOGY

Clinical Cancer Research Pub Date : 2025-01-21 DOI:10.1158/1078-0432.ccr-24-3128

Husam A Alqaisi,David E Cohn,Jing-Yi Chern,Linda R Duska,Andrea Jewell,Bradley R Corr,Ira Seth Winer,Eugenia Girda,Marta A Crispens,Neesha C Dhani,Ainhoa Madariaga,Robert C Grant,Matthew Malaguti,Crystal Lee,Valerie Bowering,Horace Wong,Andrew Poothullil,Vanessa Speers,Lisa Wang,Philippe L Bedard,John C Brady,Andrew B Nixon,Li Chen,Claire O'Connor,William Zamboni,Tawyna McKee,Jeffrey A Moscow,Amit M Oza,Stephanie Lheureux

{"title":"Randomized phase II study of bevacizumab with weekly anetumab ravtansine or weekly paclitaxel in platinum-resistant/refractory high grade ovarian cancer (NCI trial).","authors":"Husam A Alqaisi,David E Cohn,Jing-Yi Chern,Linda R Duska,Andrea Jewell,Bradley R Corr,Ira Seth Winer,Eugenia Girda,Marta A Crispens,Neesha C Dhani,Ainhoa Madariaga,Robert C Grant,Matthew Malaguti,Crystal Lee,Valerie Bowering,Horace Wong,Andrew Poothullil,Vanessa Speers,Lisa Wang,Philippe L Bedard,John C Brady,Andrew B Nixon,Li Chen,Claire O'Connor,William Zamboni,Tawyna McKee,Jeffrey A Moscow,Amit M Oza,Stephanie Lheureux","doi":"10.1158/1078-0432.ccr-24-3128","DOIUrl":null,"url":null,"abstract":"PURPOSE\r\nMesothelin (MSLN) is highly expressed in high grade serous/ endometrioid ovarian cancers (HGOC). Anetumab ravtansine (AR) is an antibody drug conjugate directed at MSLN antigen with a tubulin polymerization inhibitor. We assessed safety, activity and pharmacokinetics of the combination AR/bevacizumab (Bev) (ARB) versus weekly paclitaxel (wP)/Bev (PB) in patients with platinum resistant/refractory HGOC (prrHGOC). Expiremental design: Following a run-in phase I study to assess ARB safety, prrHGOC patients with centrally confirmed MSLN positive expression were randomized to ARB or PB (wP 80mg/m2 with Bev 10mg/kg biweekly). Patients were stratified by platinum resistance/refractory and prior Bev. The primary endpoint was progression-free survival (PFS), secondary endpoints were overall response rate (ORR), safety, and blood-based angiome biomarker assessment. A futility analysis was planned after 35 PFS events.\r\n\r\nRESULTS\r\nThe combination of Bev (10mg/kg) biweekly with AR (2.2mg/kg) weekly was well tolerated. Regarding phase II results, mesothelin positivity was 88% and 57 pts were randomized (28 ARB, 29 PB). 42% pts received prior Bev and 23% were platinum refractory. At futility analysis, the median PFS was 5.3 and 12.7 months for ARB and PB respectively (p=0.03, HR= 2.02 [1.06-3.86]). ORR was 21% with ARB and 65% with PB. The most common treatment-related grade ≥ 3 adverse events were anemia (18%) with ARB, and neutropenia (24%) with PB. Higher baseline levels of circulating IL-6 were associated with worse PFS, and its levels decreased with PB treatment.\r\n\r\nCONCLUSION\r\nOur study stopped at interim analysis highlighting the benefit of PB in prrHGOC as standard of care.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"205 1","pages":""},"PeriodicalIF":10.0000,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1158/1078-0432.ccr-24-3128","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

PURPOSE Mesothelin (MSLN) is highly expressed in high grade serous/ endometrioid ovarian cancers (HGOC). Anetumab ravtansine (AR) is an antibody drug conjugate directed at MSLN antigen with a tubulin polymerization inhibitor. We assessed safety, activity and pharmacokinetics of the combination AR/bevacizumab (Bev) (ARB) versus weekly paclitaxel (wP)/Bev (PB) in patients with platinum resistant/refractory HGOC (prrHGOC). Expiremental design: Following a run-in phase I study to assess ARB safety, prrHGOC patients with centrally confirmed MSLN positive expression were randomized to ARB or PB (wP 80mg/m2 with Bev 10mg/kg biweekly). Patients were stratified by platinum resistance/refractory and prior Bev. The primary endpoint was progression-free survival (PFS), secondary endpoints were overall response rate (ORR), safety, and blood-based angiome biomarker assessment. A futility analysis was planned after 35 PFS events. RESULTS The combination of Bev (10mg/kg) biweekly with AR (2.2mg/kg) weekly was well tolerated. Regarding phase II results, mesothelin positivity was 88% and 57 pts were randomized (28 ARB, 29 PB). 42% pts received prior Bev and 23% were platinum refractory. At futility analysis, the median PFS was 5.3 and 12.7 months for ARB and PB respectively (p=0.03, HR= 2.02 [1.06-3.86]). ORR was 21% with ARB and 65% with PB. The most common treatment-related grade ≥ 3 adverse events were anemia (18%) with ARB, and neutropenia (24%) with PB. Higher baseline levels of circulating IL-6 were associated with worse PFS, and its levels decreased with PB treatment. CONCLUSION Our study stopped at interim analysis highlighting the benefit of PB in prrHGOC as standard of care.

查看原文本刊更多论文

贝伐单抗联合阿奈单抗拉坦辛或紫杉醇治疗铂耐药/难治性高级别卵巢癌的随机II期研究（NCI试验）。

目的：内皮素（MSLN）在高级别浆液性/子宫内膜样卵巢癌（HGOC）中高表达。Anetumab ravtansine （AR）是一种针对MSLN抗原的抗体药物偶联物，具有微管蛋白聚合抑制剂。我们在铂耐药/难治性HGOC （prrHGOC）患者中评估了AR/贝伐单抗（Bev）（ARB）联合治疗与每周紫杉醇(wP)/Bev （PB）联合治疗的安全性、活性和药代动力学。实验设计：在一项评估ARB安全性的I期临床研究之后，中心确认MSLN阳性表达的prrHGOC患者被随机分配到ARB或PB组（wP 80mg/m2, Bev 10mg/kg，两周一次）。患者按铂耐药/难治和既往Bev进行分层。主要终点是无进展生存期（PFS），次要终点是总缓解率（ORR）、安全性和基于血液的血管组生物标志物评估。计划在35例PFS事件后进行无效分析。结果Bev （10mg/kg）双周联合AR （2.2mg/kg）双周耐受性良好。关于II期结果，间皮素阳性为88%，57例患者被随机分配（28例ARB， 29例PB）。42%的患者接受了先前的Bev治疗，23%的患者是铂难治的。在无效分析中，ARB和PB的中位PFS分别为5.3和12.7个月（p=0.03， HR= 2.02[1.06-3.86]）。ARB组的ORR为21%，PB组为65%。最常见的治疗相关≥3级不良事件是ARB患者贫血（18%）和PB患者中性粒细胞减少（24%）。较高的循环IL-6基线水平与较差的PFS相关，其水平随PB治疗而降低。结论：我们的研究结束于中期分析，强调了在prrHGOC中使用PB作为标准治疗的益处。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Clinical Cancer Research 医学-肿瘤学

CiteScore

20.10

自引率

1.70%

发文量

1207

审稿时长

2.1 months

期刊介绍： Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.