Ovarian cancer is a devastating disease, particularly in cases of platinum-resistant advanced stages. However, a recent early-phase trial has shown promising results in the treatment of heavily pretreated, platinum-resistant advanced ovarian cancer. The use of raludotatug deruxtecan (R-DXd), an antibody drug conjugate (ADC) directed against cadherin 6 (CDH6), has led to an “exciting” response rate, as reported by Kathleen Moore, MD, of the Stephenson Cancer Center at the University of Oklahoma.
Response Rates and Findings
In a subgroup analysis of the phase I study, the overall response rate was found to be 48.6%, with one complete response and 17 partial responses among the 37 evaluable patients treated with R-DXd. The disease control rate stood at an impressive 97.4%, with a median duration of response at 11.2 months. The time to response was 5.7 weeks, and the median progression-free survival was 8.1 months. These results showcase the potential of R-DXd in treating advanced ovarian cancer, particularly in cases where previous treatments have failed.
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. The composition of R-DXd, which includes a humanized anti-CDH6 IgG1 monoclonal antibody linked to a topoisomerase I inhibitor payload through a tetrapeptide-based cleavable linker, has shown efficacy in patients who had prior taxane and platinum therapies. The trial enrolled patients with advanced epithelial ovarian cancer, with a majority having platinum-resistant disease, and who had previously undergone multiple lines of treatment.
While the response rates with R-DXd are promising, the safety profile of the treatment is also an important consideration. The trial reported that 93.3% of patients experienced any-grade treatment-emergent adverse events (TEAEs), with grade ≥3 TEAEs reported in 44.4% of patients. The most common any-grade TEAEs included nausea, vomiting, fatigue, and diarrhea. Importantly, drug-related interstitial lung disease/pneumonitis was reported in two patients, both of which were grade 2 and resolved with intervention. Overall, the treatment was well-tolerated, with a low percentage of patients requiring discontinuation, interruption, or dose reduction.
Future Directions
Moving forward, R-DXd will be further evaluated in patients with platinum-resistant ovarian cancer in the phase II/III REJOICE-Ovarian01 trial. This continuation of the research will provide crucial insights into the long-term efficacy and safety of R-DXd in a larger patient population. The results of this ongoing trial will be instrumental in determining the future role of R-DXd in the treatment landscape of ovarian cancer.
The use of R-DXd in treating heavily pretreated, platinum-resistant advanced ovarian cancer has shown promising results in terms of response rates and disease control. The targeting of CDH6 with this ADC has demonstrated efficacy in a subgroup of patients, offering hope for those facing limited treatment options. As further research progresses, the potential for R-DXd to become a valuable addition to the treatment armamentarium for ovarian cancer continues to grow.