In a recent early-phase trial, treatment with raludotatug deruxtecan (R-DXd) has shown to lead to an “exciting” response rate among patients with heavily pretreated, platinum-resistant advanced ovarian cancer. An antibody drug conjugate (ADC) directed against cadherin 6 (CDH6), R-DXd resulted in one complete response and 17 partial responses among 37 evaluable patients, with an overall response rate of 48.6%. These findings were presented by Kathleen Moore, MD, at the Society of Gynecologic Oncology (SGO) annual meeting, where they were met with interest and enthusiasm from the medical community.
Targeting CDH6 for Efficacy in Ovarian Cancer
CDH6 is a transmembrane protein that is highly overexpressed in epithelial ovarian cancer, making it a promising target for treatment with ADCs like R-DXd. This trial included patients with advanced epithelial ovarian cancer who had received prior taxane and platinum therapies. The study population was representative, with more than half of the patients being ages 65 and older, highlighting the relevance of this research in addressing unmet medical needs in the field of ovarian cancer treatment.
In assessing the tolerability of R-DXd at various doses ranging from 1.6-9.6 mg/kg, the trial found that higher doses, such as 8.0 mg/kg, were associated with increased risk-to-benefit ratios and were eventually closed. Patients who received R-DXd at 4.8-6.4 mg/kg showed promising response rates and disease control. The safety profile of R-DXd revealed that treatment-emergent adverse events were experienced by a majority of patients, with common side effects including nausea, vomiting, fatigue, and diarrhea. Despite these effects, R-DXd was generally well-tolerated, with manageable adverse events that did not significantly impact treatment continuation.
Preliminary biomarker assessment showed that R-DXd was active in tumors with varying levels of CDH6 expression, indicating potential efficacy across different patient populations. However, further research is needed to establish a correlation between CDH6 expression and treatment response. Moving forward, R-DXd will be further evaluated in the phase II/III REJOICE-Ovarian01 trial, focusing on patients with platinum-resistant ovarian cancer to continue exploring its therapeutic potential in this challenging disease.
The early-phase trial of R-DXd in patients with heavily pretreated, platinum-resistant advanced ovarian cancer has demonstrated exciting response rates and disease control, showcasing the potential of ADCs targeting CDH6 in this patient population. While there are challenges in terms of tolerability and adverse events, the overall efficacy and promise of R-DXd in addressing unmet medical needs in ovarian cancer treatment cannot be understated. Continued research and clinical trials will provide further insights into the role of R-DXd and other ADCs in improving outcomes for patients with advanced ovarian cancer, highlighting the importance of innovation and targeted therapies in oncology.
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