Dr Moore on Ongoing ADC Development in Ovarian Cancer

"There are a number of [ADCs] that are vying for a spot in the [ovarian cancer treatment] paradigm. We're going to see some big shifts in the sequencing of these medicines in the platinum-resistant space, and we will also see the incorporation of some of these medications into earlier lines of therapy."

Kathleen N. Moore, MD, MS, professor, Section of Gynecologic Oncology, associate director, Clinical Research, Stephenson Cancer Center, director, Oklahoma TSET Phase I Program, University of Oklahoma College of Medicine, The University of Oklahoma Health Sciences, discusses novel antibody-drug conjugates (ADCs) under investigation in ovarian cancer.

The development of ADCs in the ovarian cancer therapeutic landscape is gaining traction, with several agents targeting novel antigens, utilizing diverse payloads, and employing advanced linker technology advancing to late-phase trials, Moore begins. Among these, raludotatug deruxtecan (DS-6000), a CDH6-targeting ADC with a deruxtecan payload, is currently in phase 2/3 testing, she says. Additionally, rinatabart sesutecan (PRO1184), an FRα-targeted ADC with an exatecan payload, offers a camptothecin payload distinct from the microtubule toxin payload of mirvetuximab soravtansine-gynx (Elahere), Moore reports. These agents could potentially be sequenced in treatment regimens due to their differing mechanisms of action, she notes.

Eerging ADCs, including TROP2-directed agents and TORL-1-23, which targets Claudin-6 with a microtubule toxin payload, have shown activity in phase 1 expansion cohorts, Moore continues. These advances suggest that ADCs may soon occupy a larger role in the ovarian cancer treatment landscape, particularly in the platinum-resistant setting, she states. Furthermore, their incorporation into earlier lines of therapy is under exploration, including the platinum-sensitive setting, where head-to-head trials against platinum agents are needed to determine efficacy, Moore adds.

Maintenance therapy represents another area of development for ADCs, though questions remain about long-term tolerability, resistance mechanisms, and sequencing in later lines of therapy, Moore says. The evolving paradigm for ADC use in ovarian cancer highlights the potential for these agents to transform treatment strategies, offering new avenues for both monotherapy and combination approaches across various disease stages, she concludes.