A recent phase I study revealed exciting results for patients with heavily pretreated, platinum-resistant advanced ovarian cancer who were treated with raludotatug deruxtecan (R-DXd). The study, led by Kathleen Moore, MD, showed a remarkable overall response rate of 48.6% among patients who received R-DXd, an antibody drug conjugate (ADC) directed against cadherin 6 (CDH6). The trial included a total of 37 evaluable patients, with one complete response and 17 partial responses observed. This data presents promising signals of efficacy in the treatment of ovarian cancer, marking a significant advancement in the field.
Addressing Unmet Medical Needs
The response rate of nearly 50% seen in the study has been described as “incredibly exciting” by experts in the field. Dr. Carol Aghajanian of Memorial Sloan Kettering Cancer Center highlighted the importance of this achievement, emphasizing that there is still an unmet medical need in treating patients with advanced ovarian cancer, especially those with platinum-resistant disease. The study showcased a representative population, including patients aged 65 and older, reflecting the real-world scenario in which more patients are expected to present with advanced age and challenging disease characteristics.
CDH6, the target of R-DXd, is a transmembrane protein that is highly overexpressed in epithelial ovarian cancer, making it a promising target for ADC therapy. The structure of R-DXd involves a humanized anti-CDH6 IgG1 monoclonal antibody linked to a topoisomerase I inhibitor payload through a cleavable linker. This innovative design allows for targeted delivery of the cytotoxic payload to cancer cells overexpressing CDH6, enhancing the efficacy of the treatment.
Despite demonstrating promising efficacy, R-DXd was associated with some treatment-related adverse events in the study. The most common any-grade adverse events reported included nausea, vomiting, fatigue, and diarrhea. Hematologic adverse events, such as anemia, were also observed, albeit at lower frequencies. Importantly, drug-related interstitial lung disease/pneumonitis occurred in two patients, both of which were manageable and resolved with appropriate intervention. Overall, R-DXd was well-tolerated, with a low rate of treatment discontinuation, dose interruption, and dose reduction.
Future Directions
The encouraging results of the phase I trial have paved the way for further evaluation of R-DXd in patients with platinum-resistant ovarian cancer. The ongoing phase II/III REJOICE-Ovarian01 trial aims to build on the promising signals of efficacy seen in the initial study and provide additional data on the safety and efficacy of R-DXd in a larger patient population. Continued research and development in this area hold the potential to address the unmet medical needs of patients with advanced ovarian cancer and improve outcomes in this challenging disease setting.
The early-phase trial of R-DXd in patients with heavily pretreated, platinum-resistant advanced ovarian cancer has demonstrated exciting response rates and promising signals of efficacy. The innovative mechanism of action, coupled with the well-tolerated safety profile, positions R-DXd as a potential treatment option for patients with this challenging disease. As research progresses and additional clinical data becomes available, the landscape of ovarian cancer treatment may be transformed, offering new hope to patients facing this difficult diagnosis.
Leave a Reply