Alvarez Secord A, Lewin S N, Murphy C G, Cecere S C, Barquín A, Gálvez-Montosa F, Mathews C A, Konecny G E, Ray-Coquard I, Oaknin A, Rubio Pérez M J, Bonaventura A, Diver E J, Ayuk S-M, Wang Y, Corr B R, Salutari V
Duke Cancer Institute, Duke University School of Medicine, Durham, USA.
Holy Name Medical Center Regional Cancer Center, Teaneck, USA.
Ann Oncol. 2025 Mar;36(3):321-330. doi: 10.1016/j.annonc.2024.11.011. Epub 2024 Nov 29.
Mirvetuximab soravtansine-gynx (MIRV) is a first-in-class, folate receptor alpha (FRα)-targeting antibody-drug conjugate with United States Food and Drug Administration approval for FRα-positive platinum-resistant ovarian cancer. PICCOLO is a phase II, 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).
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 (e.g. platinum-free interval) and treatment history [e.g. prior bevacizumab and poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitor (PARPi) treatment] were exploratory.
Seventy-nine participants were enrolled and efficacy assessable. The primary endpoint was met; ORR was 51.9% [95% confidence interval (CI) 40.4% to 63.3%]. Median DOR was 8.25 months (95% CI 5.55-10.78 months) and median PFS was 6.93 months (95% CI 5.85-9.59 months). OS was not mature at data cut-off. ORR was 45.8% (95% CI 32.7% to 59.2%) in participants with PD while on/within 30 days of prior PARPi (n = 59) and 60.0% (95% CI 14.7% to 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%).
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 (NCT05041257).
Mirvetuximab soravtansine-gynx（MIRV）是首个获批的靶向叶酸受体α（FRα）的抗体药物偶联物，已获美国食品药品监督管理局批准用于治疗FRα阳性的铂耐药卵巢癌。PICCOLO是一项II期全球开放标签单臂试验，评估MIRV作为三线或更后线（≥3L）治疗方案，用于治疗FRα阳性（≥75%的细胞染色强度≥2+）的复发性铂敏感卵巢癌（PSOC）患者。
参与者接受MIRV（每3周6mg/kg调整后的理想体重）治疗，直至疾病进展（PD）、出现不可接受的毒性、撤回同意或死亡。主要终点是研究者评估的客观缓解率（ORR）。关键次要终点是研究者评估的缓解持续时间（DOR）。其他终点包括研究者评估的无进展生存期（PFS）、总生存期（OS）和安全性。按疾病特征（如无铂间期）和治疗史[如既往使用贝伐单抗和聚（二磷酸腺苷[ADP] - 核糖）聚合酶抑制剂（PARPi）治疗]进行亚组分析为探索性分析。
79名参与者入组并可进行疗效评估。达到主要终点；ORR为51.9%[95%置信区间（CI）40.4%至63.3%]。中位DOR为8.25个月（95%CI 5.55 - 10.78个月），中位PFS为6.93个月（95%CI 5.85 - 9.59个月）。在数据截止时OS尚未成熟。在既往接受PARPi治疗且在治疗期间或治疗后30天内出现PD的参与者中（n = 59），ORR为45.8%（95%CI 32.7%至59.2%），在既往接受PARPi治疗但未出现PD的参与者中（n = 5），ORR为60.0%（95%CI 14.7%至94.7%）。未出现新的安全信号；最常见的治疗中出现的不良事件（TEAE）是胃肠道、神经感觉和可缓解的眼部事件。TEAE导致13名参与者（16%）停药，2名参与者（3%）死亡。
MIRV作为≥3L治疗方案用于经过大量预处理的复发性FRα阳性PSOC患者，显示出显著疗效和可耐受的安全性，包括在既往接受PARPi治疗且在治疗期间或治疗后30天内出现PD的患者中（NCT05041257）。
