Raludotatug Deruxtecan: First-in-Class CDH6 ADC Earns FDA Breakthrough Status
The FDA has granted Breakthrough Therapy Designation to Raludotatug Deruxtecan (R-DXd), a CDH6-targeting ADC, for patients with platinum-resistant ovarian, primary peritoneal, or fallopian tube cancers. Early-phase trials show ORR 46% and DCR 98%.
The U.S. FDA has granted Breakthrough Therapy Designation (BTD) to raludotatug deruxtecan (R-DXd, DS-6000) for adult patients with platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancers expressing CDH6 and previously treated with bevacizumab. This BTD underscores the potential of R-DXd as a novel treatment for a population with high unmet medical need.
Target & Mechanism: R-DXd is a CDH6-targeting antibody-drug conjugate (ADC) linked to a topoisomerase I inhibitor payload, enabling selective cytotoxicity in CDH6-expressing tumor cells.
Company & Collaboration: Developed by Daiichi Sankyo in collaboration with Merck (MSD). The collaboration was formalized in October 2023, under which Merck committed $4 billion upfront and $1.5 billion in staged continuation payments for R-DXd and two other DXd-based ADCs. Daiichi Sankyo is additionally eligible for up to $5.5 billion in sales milestones per ADC, making the total potential value of the collaboration approximately $22 billion.
Clinical Data:
- Phase 1 (NCT03870667): Among 50 patients with measurable disease, R-DXd achieved an objective response rate (ORR) of 46% and a disease control rate of 98%. Median duration of response was 11.2 months; median progression-free survival 7.9 months.
- Ongoing: REJOICE-Ovarian01 Phase 2/3 trial continues to evaluate efficacy and safety. Early results indicate promising antitumor activity with manageable safety.
Significance: R-DXd represents a first-in-class targeted therapy for CDH6-expressing platinum-resistant ovarian cancers, a population with few treatment options. The BTD may accelerate regulatory review and facilitate earlier patient access.
Next Steps: Daiichi Sankyo and Merck are advancing REJOICE-Ovarian01 to generate confirmatory Phase 2/3 data to support potential U.S. registration.
The R-DXd program and related DXd-based ADCs from Daiichi Sankyo/Merck are summarized below:
| Drug | Target | Mechanism | Indication | Stage | Key Data | Company | Deal/Notes |
|---|---|---|---|---|---|---|---|
| Raludotatug deruxtecan (R-DXd, DS-6000) | CDH6 | ADC, Topoisomerase I inhibitor payload | Platinum-resistant epithelial ovarian, primary peritoneal, fallopian tube cancers | Phase 2/3 (REJOICE-Ovarian01), FDA BTD | Phase 1 ORR 46%, DCR 98%, median DoR 11.2 mo, PFS 7.9 mo | Daiichi Sankyo / Merck | Merck collaboration: $4B upfront, $1.5B staged payments, up to $5.5B sales milestones per ADC; total potential $22B |
| Ifinatamab deruxtecan (I-DXd) | TBC | ADC, Topoisomerase I inhibitor payload | Solid tumors | Early / Phase 1 | Early efficacy signals | Daiichi Sankyo / Merck | Part of same $4B upfront deal |
| Patritumab deruxtecan (HER3-DXd) | HER3 | ADC, Topoisomerase I inhibitor payload | Solid tumors | Early / Phase 1 | Early efficacy signals |
Sources
- Merck. 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. Merck News Center. 2025.
- Daiichi Sankyo. Raludotatug Deruxtecan Continues to Demonstrate Promising Clinical Activity in Patients with Advanced Ovarian Cancer in Early Trial. Daiichi Sankyo Press Releases. 2025.