The Efficacy and Safety of Mirvetuximab Soravtansine in FRα-Positive, Third-Line and Later, Recurrent Platinum-Sensitive Ovarian Cancer: The Single-Arm Phase 2 PICCOLO Trial.
A Alvarez Secord, S N Lewin, C G Murphy, S C Cecere, A Barquín, F Gálvez-Montosa, C A Mathews, G E Konecny, I Ray-Coquard, A Oaknin, M J Rubio Pérez, A Bonaventura, E J Diver, S-A Ayuk, Y Wang, B R Corr, V Salutari
{"title":"The Efficacy and Safety of Mirvetuximab Soravtansine in FRα-Positive, Third-Line and Later, Recurrent Platinum-Sensitive Ovarian Cancer: The Single-Arm Phase 2 PICCOLO Trial.","authors":"A Alvarez Secord, S N Lewin, C G Murphy, S C Cecere, A Barquín, F Gálvez-Montosa, C A Mathews, G E Konecny, I Ray-Coquard, A Oaknin, M J Rubio Pérez, A Bonaventura, E J Diver, S-A Ayuk, Y Wang, B R Corr, V Salutari","doi":"10.1016/j.annonc.2024.11.011","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Mirvetuximab soravtansine-gynx (MIRV) is a first-in-class, folate receptor alpha (FRα)-targeting antibody-drug conjugate with US Food and Drug Administration approval for FRα-positive platinum-resistant ovarian cancer. PICCOLO is a phase 2, global, open-label, single-arm trial of MIRV as third-line or greater (≥3L) treatment in patients with FRα-positive (≥75% of cells with ≥2+ staining intensity) recurrent platinum-sensitive ovarian cancer (PSOC).</p><p><strong>Patients and methods: </strong>Participants received MIRV (6 mg/kg adjusted ideal body weight every 3 weeks) until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death. Primary endpoint was investigator-assessed objective response rate (ORR). Key secondary endpoint was investigator-assessed duration of response (DOR). Additional endpoints included investigator-assessed progression-free survival (PFS), overall survival (OS), and safety. Analyses of subgroups by disease characteristics (eg, platinum-free interval) and treatment history (eg, prior bevacizumab and poly [ADP-ribose] polymerase inhibitor [PARPi] treatment), were exploratory.</p><p><strong>Results: </strong>Seventy-nine participants were enrolled and efficacy evaluable. The primary endpoint was met; ORR was 51.9% (95% CI, 40.4-63.3). Median DOR was 8.25 months (95% CI, 5.55-10.78) and median PFS was 6.93 months (95% CI, 5.85-9.59). OS was not mature at data cutoff. ORR was 45.8% (95% CI, 32.7-59.2) in participants with PD while on/within 30 days of prior PARPi (n=59) and 60.0% (95% CI, 14.7-94.7) in those without PD with prior PARPi (n=5). No new safety signals occurred; most common treatment-emergent adverse events (TEAEs) were gastrointestinal, neurosensory, and resolvable ocular events. TEAEs led to discontinuation in 13 participants (16%) and death in 2 participants (3%).</p><p><strong>Conclusions: </strong>MIRV as ≥3L treatment in heavily pretreated recurrent FRα-positive PSOC demonstrated notable efficacy and tolerable safety, including among those with prior PD on or within 30 days of PARPi. (Funding, ImmunoGen, Inc; NCT05041257).</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7000,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.annonc.2024.11.011","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
Background: Mirvetuximab soravtansine-gynx (MIRV) is a first-in-class, folate receptor alpha (FRα)-targeting antibody-drug conjugate with US Food and Drug Administration approval for FRα-positive platinum-resistant ovarian cancer. PICCOLO is a phase 2, global, open-label, single-arm trial of MIRV as third-line or greater (≥3L) treatment in patients with FRα-positive (≥75% of cells with ≥2+ staining intensity) recurrent platinum-sensitive ovarian cancer (PSOC).
Patients and methods: Participants received MIRV (6 mg/kg adjusted ideal body weight every 3 weeks) until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death. Primary endpoint was investigator-assessed objective response rate (ORR). Key secondary endpoint was investigator-assessed duration of response (DOR). Additional endpoints included investigator-assessed progression-free survival (PFS), overall survival (OS), and safety. Analyses of subgroups by disease characteristics (eg, platinum-free interval) and treatment history (eg, prior bevacizumab and poly [ADP-ribose] polymerase inhibitor [PARPi] treatment), were exploratory.
Results: Seventy-nine participants were enrolled and efficacy evaluable. The primary endpoint was met; ORR was 51.9% (95% CI, 40.4-63.3). Median DOR was 8.25 months (95% CI, 5.55-10.78) and median PFS was 6.93 months (95% CI, 5.85-9.59). OS was not mature at data cutoff. ORR was 45.8% (95% CI, 32.7-59.2) in participants with PD while on/within 30 days of prior PARPi (n=59) and 60.0% (95% CI, 14.7-94.7) in those without PD with prior PARPi (n=5). No new safety signals occurred; most common treatment-emergent adverse events (TEAEs) were gastrointestinal, neurosensory, and resolvable ocular events. TEAEs led to discontinuation in 13 participants (16%) and death in 2 participants (3%).
Conclusions: MIRV as ≥3L treatment in heavily pretreated recurrent FRα-positive PSOC demonstrated notable efficacy and tolerable safety, including among those with prior PD on or within 30 days of PARPi. (Funding, ImmunoGen, Inc; NCT05041257).
期刊介绍：
Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine.
The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings.
Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
