Safety and activity findings from a phase 1b escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with carboplatin in patients with platinum-sensitive ovarian cancer

Gynecol Oncol. 2018 Oct;151(1):46-52. doi: 10.1016/j.ygyno.2018.07.017. Epub 2018 Aug 6.

Abstract

Purpose: To evaluate the safety profile and preliminary antitumor activity of mirvetuximab soravtansine when administered in combination with carboplatin to relapsed ovarian cancer patients.

Methods: Patients with recurrent, platinum-sensitive epithelial ovarian or fallopian tube cancer were enrolled. Eligibility included a minimum requirement of tumor FRα positivity (≥25% of cells with ≥2+ staining intensity). Patients received escalating doses of mirvetuximab soravtansine and carboplatin on day 1 of a 21-day cycle (once every 3 weeks). Mirvetuximab soravtansine maintenance therapy was permitted, at the investigators discretion, following cessation of carboplatin treatment. Adverse events, tumor response, and progression-free survival (PFS) were determined.

Results: Eighteen patients were enrolled and dosed with combination therapy; thirteen continued with mirvetuximab soravtansine maintenance following carboplatin discontinuation. Mirvetuximab soravtansine dosing was escalated from 5 to 6 mg/kg (adjusted ideal body weight) and carboplatin from AUC4 to AUC5. Adverse events were generally mild (≤ grade 2) with nausea, diarrhea, thrombocytopenia, blurred vision, and fatigue being the most common treatment-emergent toxicities. For all evaluable patients (n = 17), the confirmed objective response rate (ORR) was 71%, including three complete responses and nine partial responses, and the median PFS was 15 months. A median duration of response was not reached.

Conclusion: These data demonstrate that mirvetuximab soravtansine combined with carboplatin is a well-tolerated and highly active regimen in recurrent, platinum-sensitive ovarian cancer. Further evaluation of this combination in a randomized fashion is warranted.

Keywords: Antibody-drug conjugate; Clinical trial; Combination therapy; Ovarian cancer.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / therapeutic use
  • Cohort Studies
  • Diarrhea / chemically induced
  • Diarrhea / epidemiology
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Fallopian Tube Neoplasms / drug therapy*
  • Fallopian Tube Neoplasms / mortality
  • Fallopian Tube Neoplasms / pathology
  • Fatigue / chemically induced
  • Fatigue / epidemiology
  • Female
  • Folate Receptor 1 / antagonists & inhibitors*
  • Humans
  • Immunoconjugates / therapeutic use
  • Incidence
  • Maximum Tolerated Dose
  • Maytansine / analogs & derivatives
  • Maytansine / therapeutic use
  • Middle Aged
  • Nausea / chemically induced
  • Nausea / epidemiology
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Thrombocytopenia / chemically induced
  • Thrombocytopenia / epidemiology
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • FOLR1 protein, human
  • Folate Receptor 1
  • Immunoconjugates
  • Maytansine
  • mirvetuximab soravtansine
  • Carboplatin