A New Era for Ovarian Cancer Treatment? Raludotatug Deruxtecan Shows Promise in Platinum-Resistant Cases
A staggering 85% of women with advanced ovarian cancer will experience disease recurrence, often developing resistance to platinum-based chemotherapy – the current standard of care. But a new antibody-drug conjugate (ADC), raludotatug deruxtecan (R-DXd), is offering a beacon of hope. Data unveiled at the 2025 ESMO Congress from the phase 2/3 REJOICE-Ovarian01 trial demonstrates a remarkable 50.5% objective response rate (ORR) in patients with platinum-resistant, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer, signaling a potential paradigm shift in how we approach this challenging disease.
Targeting CDH6: A Novel Approach
What sets R-DXd apart? It’s designed to target CDH6, a protein expressed in up to 85% of epithelial ovarian tumors. This targeted approach allows the drug to deliver a potent chemotherapy payload directly to cancer cells, minimizing damage to healthy tissue. The REJOICE-Ovarian01 trial randomized 107 patients to receive R-DXd at doses of 4.8 mg/kg, 5.6 mg/kg, or 6.4 mg/kg, administered intravenously every three weeks. The primary endpoint, ORR, was evaluated by blinded independent central review, confirming the robust response observed.
Key Findings from the Phase 2 Data
The phase 2 results are particularly encouraging. Beyond the 50.5% ORR (95% CI, 40.6%–60.3%), the trial showed a median time to response of just 7.1 weeks. Importantly, the study also assessed safety and pharmacokinetics, leading researchers to identify 5.6 mg/kg as the optimal dose for the upcoming phase 3 portion of the REJOICE-Ovarian01 study. This dose demonstrated the most favorable benefit-risk profile, balancing efficacy with manageable side effects.
Navigating the Safety Profile of R-DXd
While promising, any cancer therapy must be carefully evaluated for safety. In the REJOICE-Ovarian01 trial, 93.5% of patients experienced any-grade treatment-related adverse events (TEAEs), with 35.5% being grade ≥3. However, no deaths were directly attributed to treatment-related TEAEs. Common side effects included those requiring dose modifications – treatment discontinuation (5.6%), dose reduction (18.7%), and dose delay (23.4%). A single patient experienced grade 3 or higher pneumonitis/interstitial lung disease, a potentially serious but rare complication.
Patient Characteristics and CDH6 Expression
The patient population in the phase 2 trial reflected the real-world challenges of treating platinum-resistant ovarian cancer. The median age was 60, with a significant proportion (15.9%) over 70. Over half the patients were from Europe (57.0%), with a substantial representation from Asia (42.1%). Critically, 94.1% of patients had detectable CDH6 expression at baseline, highlighting the importance of this biomarker for identifying those most likely to benefit from R-DXd. Interestingly, response rates appeared consistent regardless of the level of CDH6 expression (less than 75% vs. 75% or higher).
Looking Ahead: Phase 3 and the Future of Ovarian Cancer Treatment
The REJOICE-Ovarian01 trial is now transitioning into its phase 3 stage, comparing R-DXd at 5.6 mg/kg to physician’s choice of chemotherapy in patients with platinum-resistant ovarian cancer. This head-to-head comparison will be crucial in determining whether R-DXd can become a new standard of care. The FDA has already granted R-DXd breakthrough therapy designation, recognizing its potential to address a significant unmet need in this patient population. This designation expedites the development and review process, potentially bringing this innovative therapy to patients sooner.
The success of R-DXd underscores the growing importance of ADCs in cancer treatment. By precisely delivering cytotoxic agents to tumor cells, ADCs offer the potential for improved efficacy and reduced toxicity compared to traditional chemotherapy. As research continues to identify novel targets like CDH6, we can expect to see even more sophisticated and effective ADCs emerge, transforming the landscape of cancer care. For more information on advancements in targeted cancer therapies, explore resources from the National Cancer Institute.
What are your predictions for the role of antibody-drug conjugates in ovarian cancer treatment over the next five years? Share your thoughts in the comments below!
