Dr Lheureux on the Evolution of ADCs Since Mirvetuximab Soravtansine in Ovarian Cancer

"What is interesting [with] these new ADCs that [are] being developed is that the biomarker assessment is a little bit different. For mirvetuximab soravtansine, we know that the biomarker was based on the intensity and the percentage of expression. That [cutoff] is a little bit different with new ADCs, so [it may enable] potentially more patients to be eligible for this specific [type of] drug."

Stéphanie Lheureux, MD, PhD, clinician investigator, Cancer Clinical Research Unit, Princess Margaret Cancer Centre, discusses the evolution of antibody-drug conjugates (ADCs) since mirvetuximab soravtansine-gynx (Elahere) in ovarian cancer.

Mirvetuximab soravtansine was the first ADC to receive an indication in ovarian cancer. The drug was granted accelerated approval in November 2022 for the treatment of patients with folate receptor–alpha (FRα)–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received 1 to 3 prior lines of systemic therapy. The accelerated approval was converted to full approval in March 2024.

The approval of mirvetuximab soravtansine has set the stage for further development of ADCs in ovarian cancer, some of which contain different antigens, payloads, and linkers, Lheureux explains. She adds that patients may coexpress potential targets of interest for ADCs; this is an area in which more data are needed to determine which marker to target first in the sequence of therapy. Additional work is required to tease out whether patients who are not traditionally thought of as being chemotherapy sensitive may benefit from FRα-directed ADCs given that FRα expression may be expressed outside of high-grade histology, Lheureux says.

As research continues, it will be interesting to see whether biomarkers of response are needed for new ADCs as with mirvetuximab soravtansine. If the efficacy of newer ADCs is not tied to a specific expression threshold, that may potentially extend the reach of these agents to patients who would have previously been ineligible to receive them, Lheureux explains. Ultimately, more time is needed to better understand and weigh the safety and efficacy of these agents, Lheureux adds. To that end, significant work is underway to define the optimal dose that is needed for these agents, Lheureux concludes.