Raludotatug Deruxtecan Demonstrates Efficacy in Ovarian Cancer Trials

In a significant advancement for cancer treatment, the antibody-drug conjugate raludotatug deruxtecan (R-DXd) has shown promising clinical activity in heavily pretreated patients suffering from platinum-sensitive ovarian cancer. This finding was presented at the European Society for Medical Oncology (ESMO) Gynaecological Cancers Congress held from June 19 to 21, 2025, in Vienna, Austria.

The study, involving a subgroup of patients with platinum-sensitive ovarian cancer, reported an impressive overall response rate (ORR) of 72.2% (95% Confidence Interval [CI], 46.5%-90.3%), all of which were partial responses (PRs). Additionally, 16.7% of participants exhibited stable disease (SD), while only one patient experienced progressive disease (PD) during the trial. Notably, for those who had previously been treated with a Poly (ADP-ribose) polymerase (PARP) inhibitor, the ORR was recorded at 58.3% (95% CI, 27.7%-84.8%).

Dr. Kathleen Moore, the lead author of the study and an associate director of clinical research at the Stephenson Cancer Center in Oklahoma City, emphasized the importance of these findings, stating, "This little study shows preliminary strong evidence of response rate in a heavily pretreated platinum-sensitive population. We would argue that this data supports further development and exploration of raludotatug deruxtecan in this population, and more to come in the near future on that."

The ongoing phase 1 trial, which is multi-part in design, has been evaluating R-DXd's efficacy and safety in patients with advanced or metastatic ovarian cancer. The trial participants were not selected based on CDH6 expression levels, which are present in 65% to 85% of ovarian cancer cases. The treatment regimen involved administering R-DXd intravenously every three weeks at varying dosage levels, with the expansion phase involving doses of 4.8 mg/kg, 5.6 mg/kg, and 6.4 mg/kg to assess safety and tolerability.

Among the 18 patients in the platinum-sensitive subgroup, the median age was 65 years. The majority were from the United States, and a significant portion had undergone multiple prior systemic therapies, averaging four. Notably, 77.8% had previous exposure to bevacizumab (Avastin) and 83.3% had received prior PARP inhibitors.

Regarding safety, all patients experienced treatment-emergent adverse effects (TEAEs), with 77.8% of these being categorized as grade 3 or higher. The most frequently reported TEAEs included nausea (50%), anemia (38.9%), and fatigue (38.9%). There were serious adverse effects reported in 27.8% of participants, with the safety profile consistent with the overall study population.

Dr. Moore's findings highlight the potential of R-DXd as a viable treatment option for patients with heavily pretreated, platinum-sensitive ovarian cancer. The study's encouraging results support continued exploration of this therapeutic strategy, aiming to improve outcomes for a patient population that often faces limited treatment options. Preliminary data from the trial suggests that R-DXd may provide a meaningful clinical benefit, particularly for those who have previously undergone multiple lines of therapy.

As the oncology community anticipates further developments, the promising results from this trial signify a hopeful step forward in the battle against ovarian cancer, which continues to challenge healthcare professionals globally. The data presented at the ESMO Congress underscores the importance of ongoing research and the need for innovative treatment solutions in oncology.