FDA Grants Breakthrough Status to Raludotatug Deruxtecan for Refractory Ovarian Cancer

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to raludotatug deruxtecan (R-DXd), a novel antibody-drug conjugate (ADC), for the treatment of patients with platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancers expressing CDH6 who have previously received bevacizumab.

This marks the first BTD for raludotatug deruxtecan, jointly developed by Daiichi Sankyo and Merck, and the second designation awarded since the companies began their oncology collaboration. Across its portfolio, Daiichi Sankyo has now secured 15 Breakthrough Therapy designations in oncology.

Addressing a Major Unmet Need

Platinum-resistant ovarian cancer remains a difficult-to-treat condition with limited therapeutic options after failure of standard chemotherapy. While anti-angiogenic therapy with bevacizumab and targeted approaches such as PARP inhibitors have extended survival for some patients, most ultimately experience disease progression.

“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,” said Ken Takeshita, MD, Global Head of R&D at Daiichi Sankyo.

Clinical Evidence Behind the Designation

The FDA’s decision was based on early clinical findings from a first-in-human phase 1 trial and ongoing data from the global REJOICE-Ovarian01 phase 2/3 study.

• Phase 1 trial: Conducted in 179 patients across Asia and North America, the trial evaluated escalating doses of raludotatug deruxtecan in heavily pretreated ovarian cancer patients. Primary endpoints included safety, tolerability, and determination of the recommended dose for expansion. Secondary efficacy measures included objective response rate (ORR), duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and pharmacokinetic analyses. Subgroup data were presented at major oncology meetings between 2023 and 2025, demonstrating encouraging antitumor activity.
• REJOICE-Ovarian01: This ongoing multicenter study is enrolling approximately 710 patients globally. Its phase 2 portion is comparing three dosing regimens to establish the optimal phase 3 dose, with ORR as the primary endpoint. The phase 3 segment pits raludotatug deruxtecan at the selected 5.6 mg/kg dose against investigator’s choice chemotherapy (paclitaxel, pegylated liposomal doxorubicin, gemcitabine, or topotecan). Dual primary endpoints include ORR and PFS assessed by blinded independent central review, with overall survival (OS) among the key secondary endpoints.

Dr. Eliav Barr, Chief Medical Officer at Merck Research Laboratories, added that the designation underscores the potential of raludotatug deruxtecan to “one day become an important option” for this patient group.

Raludotatug deruxtecan is an investigational CDH6-directed DXd ADC. CDH6 (cadherin-6) is overexpressed in ovarian and other cancers, making it an attractive target for selective drug delivery. The DXd technology, previously applied in other ADCs from Daiichi Sankyo, links a humanized antibody with a topoisomerase I inhibitor payload via a cleavable linker designed to optimize delivery and limit systemic toxicity.

Next Steps

With Breakthrough Therapy Designation, raludotatug deruxtecan will receive enhanced FDA guidance and priority review mechanisms, potentially expediting development timelines. Results from REJOICE-Ovarian01 are anticipated at an upcoming medical meeting and could form the basis of a future regulatory submission if positive.