Debra L. Richardson, MD

Debra L. Richardson, MD, Associate Professor and Chief of the Section of Gynecologic Oncology, Oklahoma TSET Phase I Program, at the Stephenson Cancer Center, University of Oklahoma, Oklahoma City, discussed the emerging field of antibody-drug conjugates at a session on platinum-resistant ovarian cancer during the Society of Gynecologic Oncology 2023 Annual Meeting on Women’s Cancer. She further commented on the data on mirvetuximab soravtansine-gynx, an antibody-drug conjugate targeting folate receptor alpha (FRα), in an interview with The ASCO Post.

“I think mirvetuximab soravtansine is a great drug. It’s personalized medicine, and for this drug, we have a way to identify patients who will benefit,” Dr. Richardson said. “It’s also well tolerated. I’ve treated some patients with this drug for years (on clinical trials). We’ve seen a 32% response rate, which is higher than we see with, for instance, weekly paclitaxel, and responses can be durable.”

Antibody-drug conjugates such as mirvetuximab soravtansine represent a complex drug platform composed of antibody, linker, and drug payload that induces cancer cell death via chemical or enzyme-mediated release of payload in the lysosomes. Along with folate receptor alpha (FRα), a number of other biomarkers are emerging for antibody-drug conjugates in development for gynecologic cancers, including HER2, NaPi2b, and Trop-2, Dr. Richardson noted.

Ongoing Trials

Mirvetuximab soravtansine and several other such compounds in development are now being studied in earlier treatment lines. This immunoconjugate is also being evaluated as a maintenance option and as a component of neoadjuvant therapy, she said, noting the following ongoing clinical trials:

• MIRASOL: phase III study of single-agent mirvetuximab soravtansine vs investigator’s choice of chemotherapy in patients with platinum-resistant advanced high-grade ovarian cancer with high FRα expression
• PICCOLO: phase II study of single-agent mirvetuximab soravtansine in platinum-sensitive high-grade advanced ovarian cancer with high FRα expression
• GLORIOSA: phase III study of mirvetuximab soravtansine plus bevacizumab vs bevacizumab alone as maintenance therapy in patients with FRα-expressing recurrent platinum-sensitive ovarian cancer who have not had disease progression after second-line platinum-based chemotherapy plus bevacizumab
• IMGN853-0420: phase II study of mirvetuximab soravtansine plus carboplatin followed by continued mirvetuximab soravtansine in recurrent platinum-sensitive high-grade ovarian cancer that progressed after one prior line of platinum-based chemotherapy.

Managing Toxicities

Joyce F. Liu, MD, MPH, discussed mirvetuximab soravtansine in a recent presentation on ovarian cancer at the National Comprehensive Cancer Network (NCCN) 2023 Annual Conference, emphasizing the need to manage toxicities. Dr. Liu is Associate Chief and Director of Clinical Research in the Division of Gynecologic Oncology, Dana-Farber Cancer Institute, and Associate Professor of Medicine at Harvard Medical School, Boston.

Joyce F. Liu, MD, MPH

“We definitely see peripheral neuropathy with this drug, so that’s something to keep in mind,” she said. “Of note, we see a large percentage of patients with ocular toxicities, including blurred vision, keratopathy, and dry eye. In fact, there is a black box warning for ocular toxicities in the [U.S. Food and Drug Administration] package label, but these ocular toxicities are reversible. There are clear guidelines about monitoring and supportive care that must be followed. If you manage them well, such as with dose reductions, they can be reversed.” 

DISCLOSURE: Dr. Richardson has received consulting fees from AstraZeneca, GSK, ImmunoGen, and Mersana Therapeutics. Dr. Liu has received consulting fees from AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Eisai, Epsila Bio, Genentech, GSK, Regeneron, and Zentalis.