Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I

K N Moore; A M Oza; N Colombo; A Oaknin; G Scambia; D Lorusso; G E Konecny; S Banerjee; C G Murphy; J L Tanyi; H Hirte; J A Konner; P C Lim; M Prasad-Hayes; B J Monk; P Pautier; J Wang; A Berkenblit; I Vergote; M J Birrer

doi:10.1016/j.annonc.2021.02.017

Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I

Ann Oncol. 2021 Jun;32(6):757-765. doi: 10.1016/j.annonc.2021.02.017. Epub 2021 Mar 2.

Authors

K N Moore¹, A M Oza², N Colombo³, A Oaknin⁴, G Scambia⁵, D Lorusso⁶, G E Konecny⁷, S Banerjee⁸, C G Murphy⁹, J L Tanyi¹⁰, H Hirte¹¹, J A Konner¹², P C Lim¹³, M Prasad-Hayes¹⁴, B J Monk¹⁵, P Pautier¹⁶, J Wang¹⁷, A Berkenblit¹⁷, I Vergote¹⁸, M J Birrer¹⁹

Affiliations

¹ Department of Obstetrics and Gynecology, Stephenson Cancer Center/University of Oklahoma Health Sciences Center, Oklahoma City, USA. Electronic address: kathleen-moore@ouhsc.edu.
² Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.
³ Department of Gynecologic Oncology, European Institute of Oncology IRCCS; University of Milan-Bicocca, Milan, Italy.
⁴ Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
⁵ Gynecology Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS Roma, Rome, Italy.
⁶ Gynecologic Oncology, Fondazione IRCCS National Cancer Institute, Milan, Italy.
⁷ Department of Obstetrics and Gynecology, University of California Los Angeles, Los Angeles, USA.
⁸ Gynaecology, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, UK.
⁹ Cancer Trials Ireland and Medical Oncology, Bon Secours Hospital, Cork, Ireland.
¹⁰ Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, USA.
¹¹ Oncology, Juravinski Cancer Centre, Hamilton, Canada.
¹² Gynecologic Oncology, Memorial Sloan Kettering Cancer Center, New York, USA.
¹³ Gynecologic Oncology, The Center of Hope Renown Regional Medical Center, Reno, USA.
¹⁴ Obstetrics and Gynecology, Icahn School of Medicine at Mount Sinai, New York, USA.
¹⁵ Gynecologic Oncology, Arizona Oncology (US Oncology Network), University of Arizona, Creighton University School of Medicine, Phoenix, USA.
¹⁶ Medicine, Gustave Roussy, Villejuif, GINECO, Villejuif, France.
¹⁷ Clinical Development, ImmunoGen, Inc., Waltham, USA.
¹⁸ Department of Obstetrics and Gynecology and Gynecological Oncology, University Hospital Leuven, Leuven Cancer Institute, Leuven, Belgium.
¹⁹ Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, USA.

PMID: 33667670
DOI: 10.1016/j.annonc.2021.02.017

Abstract

Background: Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. The randomized, open-label, phase III study FORWARD I compared MIRV and investigator's choice chemotherapy in patients with platinum-resistant epithelial ovarian cancer (EOC).

Patients and methods: Eligible patients with 1-3 prior lines of therapy and whose tumors were positive for FRα expression were randomly assigned, in a 2 : 1 ratio, to receive MIRV (6 mg/kg, adjusted ideal body weight) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary endpoint was progression-free survival [PFS, Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, blinded independent central review] in the intention-to-treat (ITT) population and in the prespecified FRα high population.

Results: A total of 366 patients were randomized; 243 received MIRV and 109 received chemotherapy. The primary endpoint, PFS, did not reach statistical significance in either the ITT [hazard ratio (HR), 0.98, P = 0.897] or the FRα high population (HR, 0.69, P = 0.049). Superior outcomes for MIRV over chemotherapy were observed in all secondary endpoints in the FRα high population including improved objective response rate (24% versus 10%), CA-125 responses (53% versus 25%), and patient-reported outcomes (27% versus 13%). Fewer treatment-related grade 3 or higher adverse events (25.1% versus 44.0%), and fewer events leading to dose reduction (19.8% versus 30.3%) and treatment discontinuation (4.5% versus 8.3%) were seen with MIRV compared with chemotherapy.

Conclusions: In patients with platinum-resistant EOC, MIRV did not result in a significant improvement in PFS compared with chemotherapy. Secondary endpoints consistently favored MIRV, particularly in patients with high FRα expression. MIRV showed a differentiated and more manageable safety profile than chemotherapy.

Trial registration: ClinicalTrials.gov NCT02631876.

Keywords: antibody-drug conjugate; chemotherapy; folate receptor alpha; mirvetuximab soravtansine; ovarian cancer.

Publication types

Clinical Trial, Phase III
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Carcinoma, Ovarian Epithelial / drug therapy
Drug Resistance, Neoplasm
Female
Humans
Immunoconjugates* / therapeutic use
Maytansine* / adverse effects
Maytansine* / analogs & derivatives
Ovarian Neoplasms* / drug therapy

Substances

Antibodies, Monoclonal, Humanized
Immunoconjugates
Maytansine
mirvetuximab soravtansine

Associated data

ClinicalTrials.gov/NCT02631876