The landscape of antibody-drug conjugate (ADC) therapy in ovarian cancer is revealing complex relationships between biomarker expression and treatment efficacy, with different targets showing varying degrees of correlation with clinical outcomes.
FR-alpha and HER2: Clear Expression-Response Correlation
Mirvetuximab soravtansine-gynx (Elahere) demonstrates a clear correlation between folate receptor-alpha (FR-α) expression levels and therapeutic response. Dr. Kathleen N. Moore, associate director of clinical research at Stephenson Cancer Center, notes that while the drug shows optimal activity in patients with high FR-α expression, it maintains effectiveness even in those with medium expression levels.
Similarly, fam-trastuzumab deruxtecan-nxki (Enhertu) has shown significant activity in HER2 3+ IHC-positive tumors, as evidenced in the DESTINY-PanTumor trials, though the patient subset was small and scoring accuracy remains challenging.
TROP2 and Emerging Targets: Evidence Still Developing
The relationship between TROP2 expression and treatment response is less clear-cut. Recent phase 2 trial data (NCT04152499) presented at the 2024 ESMO Congress suggests that immunohistochemical H score might help differentiate responders from non-responders to sacituzumab tirumotecan. However, Dr. Moore emphasizes that these findings are exploratory and based on limited patient numbers.
Promising Results from Novel ADC Targets
Raludotatug deruxtecan, targeting cadherin-6 (CDH6), has shown encouraging results in early studies. A first-in-human study (NCT04707248) reported a 46% objective response rate with a median duration of response of 11.2 months in pretreated patients with advanced and metastatic ovarian cancer. The ongoing phase 2/3 REJOICE-Ovarian01 trial (NCT06161025) is expected to provide more definitive data on biomarker requirements.
Emerging Data on B7-H4 and CLDN6
For B7-H4-directed ADCs, current data is too limited to draw firm conclusions. TORL-1-23, targeting Claudin 6 (CLDN6), has demonstrated strongest activity in CLDN6-positive tumors, though the relationship between expression thresholds and response rates requires further investigation.
Dr. Moore emphasizes that while biomarker expression clearly correlates with response for certain targets like FR-α and HER2, additional research is needed to understand the expression-response relationship for newer ADCs in development.
