Dr Naumann on Next-Generation Antibody-Drug Conjugates in Ovarian Cancer

"We need all the clinical information. That's why these meetings are so important. As we get that clinical information, [we can ask: What are the toxicities? What are the clinically relevant factors that we need to make that decision? It was through great discussion...about end points in clinical trials [that enabled us to talk through how we're going to] choose those and how [we're going to] accelerate clinical trials."

R. Wendel Naumann, MD, professor and director of gynecologic oncology research, and associate medical director of clinical trials, Levine Cancer Institute, Atrium Health, discusses next-generation antibody-drug conjugates (ADCs) in ovarian cancer.

Drug development is not always linear, Naumann, explains, citing prior work on a folate receptor–alpha (FRα)–directed ADC that did not pan out in phase 3 study. However, it has been encouraging to see that the utility of ADCs has been proven with the development and launch of mirvetuximab soravtansine (Elahare), Naumann says. He adds that second-generation iterations of these agents are making waves. One such example is the FRα-directed ADC luveltamab tazevibulin, although there are many others, some even comprised of different warheads with varying mechanisms and actions, Naumann explains. As more agents begin to come to the forefront, therapeutic sequencing will become a pressing question. For now, researchers are trying to understand these agents’ mechanisms of resistance and whether they’re caused by downregulation of the receptor or resistance to the chemotherapy warhead.

Once several ADCs become available, physicians will need to decide how best to sequence these agents, a dilemma that could become more complex in the presence of a comutated tumor. If faced with this situation, Naumann explains that one should look at the level of expression, the treatment-related toxicities of each agent, prior therapy, and how closely the patient resembles those from the pivotal trial upon which the approval or indication was based. Although the sequencing of ADCs may be a new challenge, the same pillars of decision-making following frontline therapy will likely hold, Naumann explains. Ultimately, more clinical information is needed.