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The FDA has granted Breakthrough Therapy Designation (BTD) to Merck and Daiichi Sankyo’s raludotatug deruxtecan (R-DXd), a potential first-in-class CDH6-directed DXd antibody-drug conjugate (ADC) for the treatment of adult patients with platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancers.

The BTD is for patients expressing CDH6 who have previously received bevacizumab. The designation was based on encouraging preliminary clinical results from a Phase I trial (NCT04707248) as well as the ongoing Phase II/III REJOICE-Ovarian01 trial (NCT06161025).¹

How Could R-DXd Change Treatment for Platinum-Resistant Ovarian and Related Cancers?

“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, R&D, Daiichi Sankyo, in a press 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 bevacizumab.”

Phase I Trial Overview

• The two-part, multicenter, open-label, first-in-human Phase I trial is currently evaluating the safety and efficacy of R-DXd in 179 patients with advanced ovarian cancer previously treated with platinum-based chemotherapy and a taxane.
• The study initially included patients with renal cell carcinoma who were resistant or refractory to standard therapies, but this cohort was later removed from the trial.
• The primary endpoint of part one was to assess the safety and tolerability of increasing doses of R-DXd to determine the maximum-tolerated dose.
• The primary endpoint of part two will be to further evaluate the safety and efficacy of the treatment in patients with advanced ovarian cancer and advanced renal cell carcinoma.
• Key secondary endpoints include objective response rate (ORR), duration of response (DoR), disease control rate (DCR), clinical benefit rate, time to response, and progression free survival (PFS).^1,2

REJOICE-Ovarian01 Phase II/III Trial

• The global, multicenter, randomized, open-label REJOICE-Ovarian01 trial evaluated the safety and efficacy of R-DXd therapy in approximately 710 participants with ovarian, peritoneal, or fallopian tube cancer.
• The primary endpoint of the Phase II portion was ORR by blinded independent central review (BICR).
• Key secondary endpoints included ORR by investigator assessment, PFS, DoR, DCR, and overall survival (OS).
• The dual primary endpoints for Phase III are ORR and PFS as evaluated by BICR.
• Secondary endpoints include PFS and ORR by investigator assessment, DoR and DCR assessed by both BICR and investigators, and OS.^1,3

Ovarian Cancer Facts and Prevalence

• In 2022, over 324,000 women worldwide were diagnosed with ovarian cancer. For patients with advanced disease who experience recurrence, median OS can be as short as two years, and the five-year survival rate for those with distant-stage cancer is only 31.8%.
• While the advent of targeted therapies has improved treatment options and extended survival for some patients, many still face limited choices when their tumors progress despite existing treatments.
• Approximately 70% to 80% of women with advanced ovarian cancer will see disease progression after standard platinum-based chemotherapy.
• Prognosis is especially poor for patients with platinum-resistant ovarian cancer—defined as disease progression within six months of completing their last platinum-based therapy—leaving them with very few effective treatment options.¹

“The FDA’s Breakthrough Designation is a reflection of our commitment to advancing research for patients impacted by women’s cancers,” said Eliav Barr, MD, SVP, head, global clinical development, chief medical officer, Merck Research Laboratories, in the press release. “Raludotatug deruxtecan has the potential to one day become an important option for the treatment of patients with CDH6-expressing platinum-resistant ovarian, primary peritoneal, or fallopian tube cancers previously treated with bevacizumab, and we are excited to share data from REJOICE-Ovarian01 with the scientific community at an upcoming medical meeting and to continue working closely with the FDA.”

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. Merck. September 15, 2025. Accessed September 16, 2025. https://www.merck.com/news/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-treat/
2. A Study of DS-6000a in Subjects With Advanced Renal Cell Carcinoma and Ovarian Tumors. Clinicaltrials.gov. Accessed September 16, 2025. https://clinicaltrials.gov/study/NCT04707248?term=NCT04707248&rank=1
3. A Study of Raludotatug Deruxtecan (R-DXd) in Subjects With Platinum-resistant, High-grade Ovarian, Primary Peritoneal, or Fallopian Tube Cancer. Clinicaltrials.gov. Accessed September 16, 2025. https://clinicaltrials.gov/study/NCT06161025?utm_source=chatgpt.com