The Evolving Ovarian Cancer ADC Landscape

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The antibody-drug conjugate (ADC_ landscape in ovarian cancer continues expanding with novel agents targeting folate receptor alpha and alternative antigens. Rinatabart sesutecan (Rina-S) represents a promising folate receptor—targeting ADC with a topoisomerase I payload, showing activity across various folate receptor expression levels unlike current requirements for high expression. Early phase trials demonstrate encouraging response rates around 50% with different toxicity profiles, notably lacking ocular toxicity and interstitial lung disease seen with mirvetuximab.

Multiple companies are developing folate receptor-targeting ADCs, including Lilly’s compound with potentially reduced immune activation and Chinese-developed agents showing promise in large patient cohorts. The concerning similarity in payloads across multiple ADCs raises questions about sequencing strategies and cross-resistance patterns. Novel targets like CDH6 and CAD6 offer opportunities for combination approaches or sequential therapy in patients who progress on folate receptor–targeting agents.

The future of ovarian cancer treatment likely involves multiple ADC sequencing strategies, requiring careful consideration of payload diversity and target expression patterns. Second-generation ADCs may offer improved safety profiles with maintained efficacy, addressing current limitations like pulmonary and ocular toxicities. As these agents move toward earlier treatment lines, understanding optimal combinations with current standard therapies and developing rational sequencing algorithms will be crucial for maximizing patient benefit from this rapidly expanding therapeutic class.