FDA Grants Breakthrough Status to Raludotatug Deruxtecan in Ovarian Cancer

Raludotatug deruxtecan (R-DXd) has been granted breakthrough therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancers expressing CDH6 who have received prior treatment with Avastin (bevacizumab).

“Patients have limited treatment options once ovarian cancer becomes resistant to platinum-based chemotherapy, highlighting the urgent need for new medicines that can improve patient outcomes,” Dr. Ken Takeshita, global head, R&D, Daiichi Sankyo, said in a news release. “The receipt of breakthrough therapy designation represents an important step forward in our efforts to advance raludotatug deruxtecan as a novel medicine for patients with CDH6 expressing platinum-resistant ovarian, primary peritoneal or fallopian tube cancers previously treated with [Avastin].”

R-DXd is a potential first-in-class antibody drug conjugate designed to target CDH6. It is part of the DXd antibody drug conjugate platform, specifically engineered by Daiichi Sankyo. The therapy was discovered by Daiichi Sankyo and is being jointly developed with Merck, which is known as MSD outside of the United States and Canada.

The FDA breakthrough therapy designation is intended to speed the development and regulatory review of potential new medicines for serious conditions with unmet medical needs. To qualify, a medicine must show promising early clinical results indicating a substantial improvement on a meaningful clinical endpoint compared with existing treatments.

The FDA’s decision to grant breakthrough therapy designation was supported by findings from a phase 1 trial and the ongoing REJOICE-Ovarian01 phase 2/3 trial. Results from a subgroup analysis of the phase 1 trial were first shared at the 2023 European Society for Medical Oncology meeting, with further subgroup data later presented at the 2024 Society for Gynecologic Oncology Annual Meeting on Women’s Cancer and the 2025 European Society for Medical Oncology Gynaecological Cancers Congress. This marks the first breakthrough therapy designation for R-DXd and the second designation achieved under the collaboration between Daiichi Sankyo and Merck.

In the phase 1 trial, a subgroup of 50 patients with measurable ovarian cancer treated with R-DXd (4.8 to 8 milligrams per kilogram) achieved a confirmed objective response rate of 46% by investigator assessment. Among these, one complete response, 22 partial responses and four unconfirmed responses were reported, resulting in a disease control rate of 98%. Median duration of response was 11.2 months and median progression-free survival was 7.9 months, based on data as of July 14, 2023. Responses were observed across patients with different levels of tumor CDH6 expression.

Trial Design

The two-part, multicenter, open-label, first-in-human phase 1 trial is evaluating the safety and efficacy of R-DXd in adults with advanced ovarian cancer who were previously treated with platinum-based chemotherapy and a taxane. The trial originally included patients with renal cell carcinoma resistant or refractory to standard treatment, but that portion was discontinued.

In the dose-escalation part of the study, the primary objective was to assess safety and tolerability of increasing doses to determine the maximum tolerated dose and recommended dose for expansion. The dose-expansion part is designed to further evaluate safety and efficacy in patients with advanced ovarian cancer and advanced renal cell carcinoma.

The study is assessing safety endpoints such as dose-limiting toxicities and side effects, as well as efficacy endpoints including objective response rate, duration of response, disease control rate, clinical benefit rate, time to response and progression-free survival. Pharmacokinetic and exploratory biomarker endpoints are also being studied.

The phase 1 trial enrolled 179 patients in Asia and North America. More details are available on ClinicalTrials.gov.

References

1. “Raludotatug Deruxtecan Granted Breakthrough Therapy Designation by U.S. FDA for Patients with CDH6 Expressing Platinum-Resistant Ovarian, Primary Peritoneal or Fallopian Tube Cancers Previously Treated with Bevacizumab.” DaiichiSankyo. News Release. September 15, 2025.
2. “Raludotatug Deruxtecan Continues to Demonstrate Promising Clinical Activity in Patients with Advanced Ovarian Cancer in Early Trial.” DaiichiSankyo. News Release. October 22, 2023.

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