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

Debra L Richardson; Kathleen N Moore; Ignace Vergote; Lucy Gilbert; Lainie P Martin; Gina M Mantia-Smaldone; Cesar M Castro; Diane Provencher; Ursula A Matulonis; James Stec; Yuemei Wang; Michael Method; David M O'Malley

doi:10.1016/j.ygyno.2024.01.045

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 Mar 5:185:186-193. doi: 10.1016/j.ygyno.2024.01.045. Online ahead of print.

Authors

Affiliations

¹ Stephenson Cancer Center at the University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; Sarah Cannon Research Institute, Nashville, TN, United States. Electronic address: debra-richardson@ouhsc.edu.
² Stephenson Cancer Center at the University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; Sarah Cannon Research Institute, Nashville, TN, United States. Electronic address: kathleen-moore@ouhsc.edu.
³ University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. Electronic address: ignace.vergote@uzleuven.be.
⁴ McGill University Health Center-Research Institute, Montréal, Québec, Canada. Electronic address: lucy.gilbert@mcgill.ca.
⁵ Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States. Electronic address: lainie.martin@pennmedicine.upenn.edu.
⁶ Fox Chase Cancer Center, Philadelphia, PA, United States. Electronic address: gina.mantia-smaldone@fccc.edu.
⁷ Massachusetts General Hospital, Boston, MA, United States. Electronic address: cmcastro@mgh.harvard.edu.
⁸ Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada. Electronic address: diane.provencher.med@ssss.gouv.qc.ca.
⁹ Dana-Farber Cancer Institute, Boston, MA, United States. Electronic address: ursula_matulonis@dfci.harvard.edu.
¹⁰ ImmunoGen, Inc., Waltham, MA, United States. Electronic address: james.stec@immunogen.com.
¹¹ ImmunoGen, Inc., Waltham, MA, United States. Electronic address: yuemei.wang@immunogen.com.
¹² ImmunoGen, Inc., Waltham, MA, United States. Electronic address: michael.method@immunogen.com.
¹³ The Ohio State University, James Comprehensive Cancer Center, Columbus, OH, United States. Electronic address: david.o'malley@osumc.edu.

PMID: 38447347
DOI: 10.1016/j.ygyno.2024.01.045

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.