S17 Ep39: Sequencing and Emerging Targets Revamp the Platinum-Resistant Ovarian Cancer Treatment Paradigm: With David O’Malley, MD

In today’s episode, we spoke with David O’Malley, MD. Dr O’Malley is a professor in the Department of Obstetrics and Gynecology at The Ohio State University College of Medicine and the director of the Division of Gynecologic Oncology at The Ohio State University Comprehensive Cancer Center–James in Columbus, Ohio. 

In our exclusive interview, Dr O’Malley discussed his approach to treatment selection and sequencing in platinum-resistant ovarian cancer, a disease setting he described as representing the highest unmet need in the field. He emphasized the central role of clinical trial enrollment and biomarker-driven decision-making, alongside practical patient-centered considerations, such as infusion schedule and quality of life.

He highlighted the growing importance of antibody-drug conjugates (ADCs) in this setting, noting that folate receptor alpha and HER2 are the two biomarkers most relevant to current practice. Dr O’Malley outlined how National Comprehensive Cancer Network guidelines support treatment across a broader range of expression levels than initial approvals reflected, citing emerging data suggesting activity even at lower expression thresholds. He also addressed payload sequencing, explaining that outside of a clinical trial, he currently uses topoisomerase I–based ADCs and antimicrotubule-based ADCs each one time only, and remains open to targeting the same antigen again if the payload differs.

The discussion also touched on combination strategies, resistance biology, and the evolving role of immunotherapy following the survival benefit observed with pembrolizumab (Keytruda) in the phase 3 KEYNOTE-B96 trial (NCT05116189). Dr O’Malley expressed enthusiasm for next-generation payloads, dual-target approaches, and the potential for bispecific antibodies and novel DNA damage response–targeting agents to define the post-ADC treatment landscape.

Finally, Dr O’Malley underscored the need for more tumor biopsies to better characterize resistance mechanisms and called for expanded pharmaceutical investment in retreatment and cross-resistance studies to guide future sequencing decisions.