Matulonis Ursula A, Vergote Ignace, Moore Kathleen N, Martin Lainie P, Castro Cesar M, Gilbert Lucy, Xia Yu, Method Michael, Stec James, Birrer Michael J, O'Malley David M
Dana-Farber Cancer Institute, Boston, MA, USA.
University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
Gynecol Oncol. 2025 Jul 22;200:96-104. doi: 10.1016/j.ygyno.2025.06.016.
Evaluate the efficacy and safety of mirvetuximab soravtansine-gynx (MIRV) plus pembrolizumab in dose escalation and expansion cohorts of heavily pretreated patients with platinum-resistant ovarian cancer (PROC).
Participants with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer whose disease relapsed ≤6 months from last platinum-based treatment received MIRV (6 mg/kg adjusted ideal body weight) and pembrolizumab (200 mg) intravenously once every 3 weeks. Tumor FRα expression thresholds were ≥25 % (dose escalation cohort) and ≥50 % (dose expansion cohort) of cells with ≥2+ membrane staining intensity. The primary efficacy endpoint was objective response rate (ORR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and safety.
Fifty-six participants received the doublet. Median age was 62 years (range, 40-78). Twenty percent of participants had 3 prior lines of systemic treatment, 43 % had ≥4 prior lines, 43 % had prior bevacizumab exposure, and 41 % had prior PARP inhibitor exposure. Among 55 response-evaluable participants, ORR was 31 % (95 % CI, 19-45), median DOR was 8.0 months (95 % CI, 4.2-NR), and median PFS was 4.2 months (95 % CI, 2.8-5.6). Efficacy persisted in patients with multiple prior lines of treatment. Treatment-emergent adverse events were consistent with the profiles of each agent; the most common were diarrhea (all grades, 57 %; grade 3, 4 %), nausea (55 %; 5 %), and fatigue (50 %; 2 %). Treatment-emergent pneumonitis occurred in 25 % of participants, with grade ≥3 events occurring in 2 (4 %) participants.
MIRV plus pembrolizumab demonstrated anti-cancer efficacy and a tolerable safety profile in heavily pretreated patients with PROC. However, the efficacy benefit may be mainly attributable to MIRV alone.
评估mirvetuximab soravtansine-gynx（MIRV）联合帕博利珠单抗在铂耐药卵巢癌（PROC）经大量预处理患者的剂量递增和扩展队列中的疗效和安全性。
复发性上皮性卵巢癌、输卵管癌或原发性腹膜癌患者，其疾病自上次铂类治疗后复发时间≤6个月，每3周静脉注射一次MIRV（6mg/kg调整后的理想体重）和帕博利珠单抗（200mg）。肿瘤FRα表达阈值为膜染色强度≥2+的细胞的≥25%（剂量递增队列）和≥50%（剂量扩展队列）。主要疗效终点为客观缓解率（ORR）。次要终点包括缓解持续时间（DOR）、无进展生存期（PFS）和安全性。
56名参与者接受了联合治疗。中位年龄为62岁（范围40-78岁）。20%的参与者接受过3线全身治疗，43%接受过≥4线治疗，43%曾接受过贝伐单抗治疗，41%曾接受过PARP抑制剂治疗。在55名可评估缓解的参与者中，ORR为31%（95%CI，19-45），中位DOR为8.0个月（95%CI，4.2-NR），中位PFS为4.2个月（95%CI，2.8-5.6）。在接受过多次前期治疗的患者中疗效持续存在。治疗中出现的不良事件与每种药物的特征一致；最常见的是腹泻（所有级别，57%；3级，4%）、恶心（55%；5%）和疲劳（50%；2%）。25%的参与者出现治疗中出现的肺炎，2名（4%）参与者出现≥3级事件。
MIRV联合帕博利珠单抗在经大量预处理的PROC患者中显示出抗癌疗效和可耐受安全性。然而，疗效获益可能主要归因于单独使用MIRV。
