Phase 1b study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate, in combination with carboplatin and bevacizumab in patients with platinum-sensitive ovarian cancer

Gynecol Oncol. 2024 Jun:185:186-193. doi: 10.1016/j.ygyno.2024.01.045. Epub 2024 Mar 5.

Abstract

Objective: Evaluate the antitumor activity and safety profile of the triplet combination of mirvetuximab soravtansine (MIRV), carboplatin, and bevacizumab in recurrent, platinum-sensitive ovarian cancer.

Methods: Participants with recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer (1-2 prior lines of therapy) received MIRV (6 mg/kg adjusted ideal body weight), carboplatin (AUC5), and bevacizumab (15 mg/kg) once every 3 weeks. Carboplatin could be discontinued after 6 cycles per investigator discretion; continuation of MIRV+bevacizumab as maintenance therapy was permitted. Eligibility included folate receptor alpha (FRα) expression by immunohistochemistry (≥50% of cells with ≥2+ intensity; PS2+ scoring); prior bevacizumab was allowed. Tumor response, duration of response (DOR), progression-free survival (PFS), and adverse events (AEs) were assessed.

Results: Forty-one participants received triplet therapy, with a median of 6, 12, and 13 cycles of carboplatin, MIRV, and bevacizumab, respectively. The confirmed objective response rate was 83% (9 complete and 25 partial responses). The median DOR was 10.9 months; median PFS was 13.5 months. AEs (any grade) occurred as expected, based on each agent's safety profile; most common were diarrhea (83%), nausea (76%), fatigue (73%), thrombocytopenia (71%), and blurred vision (68%). Most cases were mild to moderate (grade ≤2), except for thrombocytopenia, for which most drug-related discontinuations occurred, and neutropenia.

Conclusions: This triplet regimen (MIRV+carboplatin+bevacizumab) was highly active, with a tolerable AE profile in participants with recurrent, platinum-sensitive, FRα-expressing ovarian cancer. Thrombocytopenia was the primary cause of dose modifications. These outcomes compare favorably to historical data reported for platinum-based chemotherapy plus bevacizumab regimens in similar patient populations.

Keywords: Antibody-drug conjugate; Clinical trial; Combination therapy; Folate receptor alpha; Mirvetuximab soravtansine; Platinum-sensitive ovarian cancer.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Bevacizumab* / administration & dosage
  • Bevacizumab* / adverse effects
  • Carboplatin* / administration & dosage
  • Carboplatin* / adverse effects
  • Carcinoma, Ovarian Epithelial* / drug therapy
  • Fallopian Tube Neoplasms / drug therapy
  • Female
  • Folate Receptor 1*
  • Humans
  • Immunoconjugates* / administration & dosage
  • Immunoconjugates* / adverse effects
  • Maytansine* / administration & dosage
  • Maytansine* / adverse effects
  • Maytansine* / analogs & derivatives
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / pathology
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / pathology
  • Peritoneal Neoplasms / drug therapy
  • Progression-Free Survival
  • Thrombocytopenia / chemically induced

Substances

  • mirvetuximab soravtansine
  • Bevacizumab
  • Carboplatin
  • Folate Receptor 1
  • Maytansine
  • Antibodies, Monoclonal, Humanized
  • Immunoconjugates