Diana P. English, MD, a gynecologic oncologist at Stanford Hospital and Clinics, discusses an investigational antibody-drug conjugate (ADC) in ovarian cancer.

In addition to mirvetuximab soravtansine, there are other ADCs targeting other antigens or proteins that are overexpressed in ovarian cancer, says English. One target is mesothelin, which is expressed on the majority of ovarian cancers. The investigational ADC, anetumab ravtansine, targets the mesothelin protein. This ADC is also conjugated to the antimicrotubular agent DM4, she explains. Although the ADC has shown some promise in ovarian cancer, more meaningful responses were observed in mesothelioma. Nonetheless, a phase II trial is evaluating the use of this agent in combination with bevacizumab (Avastin) versus bevacizumab plus paclitaxel in patients with platinum-resistant disease.

The appeal of ADCs is the potential for them to be very specific to a particular target protein, or antigen overexpressed in ovarian cancer and spare normal tissue, adds English, resulting in not only better outcomes but less adverse events.

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Dr. English on an Investigational Antibody-Drug Conjugate in Ovarian Cancer

Diana P. English, MD, a gynecologic oncologist at Stanford Hospital and Clinics, discusses the development of the antibody drug conjugate (ADC) mirvetuximab soravtansine in ovarian cancer.

Mirvetuximab soravtansine targets the folate receptor-alpha (FRα), says English. This ADC has an antibody specific to the FRα. The specificity of the antibody for the FRα allows physicians to target tumor cells that tend to have a high expression of FRα, states English.

About 80% of ovarian cancers overexpress FRα, which makes it a worthwhile target to explore. In the population of patients who are platinum-resistant and not heavily pretreated, the drug has shown very meaningful results, with objective response rates around 39%. Typically, single agents show response rates in the range of 10% to 20%. The drug is now being tested in a phase III clinical trial called FORWARD I. It will be compared with physician’s choice of doxorubicin, topotecan, or paclitaxel in platinum-resistant ovarian cancer.

Diana P. English, MD

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