GLORIOSA: A randomized, open-label, phase 3 study of mirvetuximab soravtansine with bevacizumab vs. bevacizumab as maintenance in platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer.

Abstract

TPS5622 Background: Elevated folate receptor-alpha (FRα) expression is a characteristic of epithelial ovarian cancer (EOC), thereby providing a rational target for antibody drug conjugate (ADC) development in ovarian cancer. Mirvetuximab soravtansine (MIRV) is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent that has received accelerated approval for patients with FRα positive platinum resistant ovarian cancer. MIRV in combination with BEV has demonstrated clinically meaningful activity, along with acceptable tolerability, in patients with FRα expressing ovarian cancer.1 Methods: GLORIOSA is a randomized, open-label, phase 3 study designed to evaluate the efficacy of in combination with bevacizumab compared with bevacizumab alone as maintenance for patients with FRα-positive recurrent platinum-sensitive epithelial ovarian, fallopian tube, or peritoneal cancers who have not progressed after second line platinum-based chemotherapy plus bevacizumab (which may be given on protocol for patients with high FRα tumor expression). Confirmation of high FRα positivity by immunohistochemistry using the Ventana FOLR1 CDx Assay (high expression; ≥ 75% of viable tumor cells staining at 2+ intensity) and 1 prior line of therapy is required for inclusion. GLORIOSA is designed to randomize 418 patients, 1:1 receiving intravenous MIRV at a dose of 6 mg/kg adjusted ideal body weight plus bevacizumab 15mg/kg every 3 weeks or receiving bevacizumab 15mg/kg every 3 weeks until disease progression or unacceptable toxicity. Radiological assessments will be conducted every 9 weeks (± 2 weeks) for 72 weeks, and subsequently every 18 weeks (± 3 weeks) until progressive disease (PD), death, the start of new anticancer therapy, or withdrawal of consent from the study (whichever occurs first). The primary efficacy endpoint is progression-free survival by investigator and will also be assessed as a sensitivity analysis. The secondary endpoints include objective response rate, quality of life, overall survival, and safety and tolerability. GLORIOSA is a global study that opened for enrollment in December 2022. Reference: 1. Gilbert L, Oaknin A, Matulonis UA, et al. Safety and efficacy of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer. Gynecol Oncol. 2023; 170: 241–247 Clinical trial information: NCT05445778 .