Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer

N Engl J Med. 2023 Dec 7;389(23):2162-2174. doi: 10.1056/NEJMoa2309169.

Abstract

Background: Mirvetuximab soravtansine-gynx (MIRV), a first-in-class antibody-drug conjugate targeting folate receptor α (FRα), is approved for the treatment of platinum-resistant ovarian cancer in the United States.

Methods: We conducted a phase 3, global, confirmatory, open-label, randomized, controlled trial to compare the efficacy and safety of MIRV with the investigator's choice of chemotherapy in the treatment of platinum-resistant, high-grade serous ovarian cancer. Participants who had previously received one to three lines of therapy and had high FRα tumor expression (≥75% of cells with ≥2+ staining intensity) were randomly assigned in a 1:1 ratio to receive MIRV (6 mg per kilogram of adjusted ideal body weight every 3 weeks) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary end point was investigator-assessed progression-free survival; key secondary analytic end points included objective response, overall survival, and participant-reported outcomes.

Results: A total of 453 participants underwent randomization; 227 were assigned to the MIRV group and 226 to the chemotherapy group. The median progression-free survival was 5.62 months (95% confidence interval [CI], 4.34 to 5.95) with MIRV and 3.98 months (95% CI, 2.86 to 4.47) with chemotherapy (P<0.001). An objective response occurred in 42.3% of the participants in the MIRV group and in 15.9% of those in the chemotherapy group (odds ratio, 3.81; 95% CI, 2.44 to 5.94; P<0.001). Overall survival was significantly longer with MIRV than with chemotherapy (median, 16.46 months vs. 12.75 months; hazard ratio for death, 0.67; 95% CI, 0.50 to 0.89; P = 0.005). During the treatment period, fewer adverse events of grade 3 or higher occurred with MIRV than with chemotherapy (41.7% vs. 54.1%), as did serious adverse events of any grade (23.9% vs. 32.9%) and events leading to discontinuation (9.2% vs. 15.9%).

Conclusions: Among participants with platinum-resistant, FRα-positive ovarian cancer, treatment with MIRV showed a significant benefit over chemotherapy with respect to progression-free and overall survival and objective response. (Funded by ImmunoGen; MIRASOL ClinicalTrials.gov number, NCT04209855.).

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Carcinoma, Ovarian Epithelial* / drug therapy
  • Carcinoma, Ovarian Epithelial* / genetics
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Folate Receptor 1 / antagonists & inhibitors
  • Folate Receptor 1 / genetics
  • Humans
  • Immunoconjugates / administration & dosage
  • Immunoconjugates / adverse effects
  • Immunoconjugates / therapeutic use
  • Maytansine* / administration & dosage
  • Maytansine* / adverse effects
  • Maytansine* / analogs & derivatives
  • Maytansine* / therapeutic use
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Platinum Compounds / pharmacology

Substances

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

Associated data

  • ClinicalTrials.gov/NCT04209855