A recent early-phase trial has revealed an “exciting” response rate among patients with heavily pretreated, platinum-resistant advanced ovarian cancer who were treated with raludotatug deruxtecan (R-DXd). The trial showed promising outcomes, with one complete response and 17 partial responses among 37 evaluable patients who received R-DXd, an antibody drug conjugate (ADC) directed against cadherin 6 (CDH6). The overall response rate was an impressive 48.6%, showcasing the potential of this new treatment option. Moreover, the disease control rate was 97.4%, indicating a high level of efficacy in this patient population.
The use of CDH6 as a target for the ADC R-DXd is particularly interesting due to the high overexpression of this transmembrane protein in epithelial ovarian cancer. The composition of R-DXd, which includes a humanized anti-CDH6 IgG1 monoclonal antibody linked to a topoisomerase I inhibitor payload through a cleavable linker, offers a novel approach to treating this type of cancer. The trial included patients who had received prior taxane and platinum therapies, demonstrating the potential benefit of R-DXd in a heavily pretreated population.
Preliminary biomarker assessments have shown that R-DXd is active in tumors with varying levels of CDH6 expression, highlighting its potential use across a broad range of patients. However, the correlation between CDH6 expression and treatment response is yet to be fully understood. In terms of safety, the trial reported that 93.3% of patients experienced any-grade treatment-emergent adverse events (TEAEs), with grade ≥3 TEAEs occurring in 44.4% of patients. The most common TEAEs included nausea, vomiting, fatigue, and diarrhea, with anemia being the most frequent hematologic adverse event. Despite these adverse events, R-DXd was generally well-tolerated, with manageable side effects leading to treatment discontinuation in only a small percentage of patients.
Future Directions and Implications
The positive outcomes observed in this early-phase trial have paved the way for further evaluation of R-DXd in patients with platinum-resistant ovarian cancer. The upcoming phase II/III REJOICE-Ovarian01 trial will provide additional insights into the efficacy and safety profile of this novel treatment option. As the landscape of ovarian cancer treatment continues to evolve, the potential of ADCs targeting CDH6, such as R-DXd, offers hope for patients with limited treatment options. Continued research and clinical trials will be crucial in determining the long-term benefits and outcomes associated with this promising therapy.
The early-phase trial of R-DXd in platinum-resistant advanced ovarian cancer has demonstrated an exciting response rate and disease control rate, highlighting the potential of this novel ADC in addressing unmet medical needs in this patient population. With further research and evaluation, R-DXd may offer a promising treatment option for patients with advanced epithelial ovarian cancer, setting the stage for future advancements in the field of oncology.
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