On October 19, 2025 Merck and Daiichi Sankyo reported results from the phase 2 (dose optimization) part of the REJOICE-Ovarian01 phase 2/3 trial showed that raludotatug deruxtecan (R-DXd) demonstrated clinically meaningful response rates in patients with recurrent platinum-resistant ovarian, primary peritoneal or fallopian tube cancer. These data were presented today during a late-breaking proffered paper session (LBA42) at the 2025 European Society for Medical Oncology (#ESMO25) Congress.

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Raludotatug deruxtecan is a specifically engineered, potential first-in-class CDH6 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and Merck (NYSE: MRK), known as MSD outside of the United States and Canada.

The median overall survival for advanced ovarian cancer following recurrence can be as little as two years, with a five-year survival rate of 31.8% for those with distant stage disease.1,2 Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens, highlighting the need for new treatment options.3

A confirmed objective response rate (ORR) of 50.5% (95% confidence interval [CI]: 40.6-60.3) was observed in patients (n=107) with platinum-resistant ovarian cancer receiving raludotatug deruxtecan across three doses (4.8 mg/kg, 5.6 mg/kg and 6.4 mg/kg) as assessed by blinded independent central review (BICR). There were 3 complete responses (CRs) and 51 partial responses (PRs) seen, and a disease control rate (DCR) of 77.6% (95% CI: 68.5–85.1) was observed.

In patients receiving the 5.6 mg/kg dose (n=36), a confirmed ORR of 50.0% (95% CI: 32.9–67.1) was observed as assessed by BICR with two CRs (5.6%), 16 PRs (44.4%) and a DCR of 80.6% (95% CI: 64.0–91.8). Clinically meaningful tumor responses were seen irrespective of dose and across a range of CDH6 expression levels.

The safety profile of raludotatug deruxtecan observed in REJOICE-Ovarian01 is consistent with safety findings from the phase 1 trial with no new safety signals identified. Nausea, anemia, asthenia and neutropenia were the most common treatment-emergent adverse events (TEAEs) across all doses. Treatment discontinuations due to treatment-related TEAEs occurred in 8.3% (n=3), 0.0% (n=0) and 8.6% (n=3) in the 4.8 mg/kg, 5.6mg/kg and 6.4 mg/kg groups, respectively. Grade 3 or higher treatment-related TEAEs occurred in 27.8% (n=10), 30.6% (n=11), and 48.6% (n=17) of patients in the 4.8 mg/kg (n=36), 5.6 mg/kg (n=36), and 6.4 mg/kg (n=35) groups, respectively.

The most common TEAEs (≥10% of total population) in the 5.6 mg/kg cohort included nausea (69.4%), anemia (58.3%), asthenia (50.0%), neutropenia (44.4%), vomiting (33.3%), constipation (27.8%), decreased appetite (25.0%), thrombocytopenia (19.4%), AST increase (16.7%), diarrhea (16.7%) and leukopenia (13.9%). Four (3.7%) interstitial lung disease (ILD)/pneumonitis events were confirmed as treatment-related across all doses as determined by an independent adjudication committee. The majority of ILD events (one with 5.6 mg/kg, two with 6.4 mg/kg) were low grade (grade 1 or 2). One grade ≥3 (4.8 mg/kg) ILD event was reported. Based on these efficacy and safety results, the 5.6 mg/kg dose has been selected for the phase 3 part of the trial.

"When ovarian cancer becomes resistant to platinum-based chemotherapy, treatment options for patients become limited," said Isabelle Ray-Coquard, MD, PhD, President, ENGOT (European Network of Gynecological Oncology Trial) Group, Trial Leader, National Group of Investigators on the Studies of Ovarian and Breast Cancer (GINECO), and Medical Oncologist, Centre Léon Bérard, Lyon, France. "These promising results from the first part of REJOICE-Ovarian01 suggest that raludotatug deruxtecan may have an important role in treating patients with platinum-resistant ovarian cancer and support further evaluation in the phase 3 portion of this trial."

"In this dose optimization analysis, rapid responses with impressive disease control have been observed with raludotatug deruxtecan across a range of CDH6 expression levels," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "These results, which contributed to the recent Breakthrough Therapy Designation in the U.S., reinforce the potential for raludotatug deruxtecan to become a new treatment option for certain types of patients with platinum-resistant ovarian cancer."

"While we have seen targeted treatment advancements and improved outcomes in ovarian cancer in recent years, there is still a high unmet need for additional options for patients," said Eliav Barr, MD, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories. "CDH6 is highly expressed in ovarian cancer, which underscores the potential of raludotatug deruxtecan to make an impact."

In September 2025, raludotatug deruxtecan was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration 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 bevacizumab.

Median follow-up for the 4.8-mg/kg, 5.6-mg/kg and 6.4-mg/kg cohorts was 5.6 months (95% CI: 4.7–6.3), 5.6 months (95% CI: 4.6–5.8), and 5.2 months (95% CI: 4.9–5.8), respectively. A majority of patients (51.4%) in REJOICE-Ovarian01 received three prior lines of treatment, including bevacizumab (n=89; 83.2%), PARP inhibitor (n=75; 70.1%) and mirvetuximab soravtansine (n=3; 2.8%). As of the data cut-off of February 26, 2025, 66 patients (61.7%) remain on treatment with raludotatug deruxtecan.

Summary of REJOICE-Ovarian01 Results

Efficacy Measure

Raludotatug
Deruxtecan
Across 4.8, 5.6 and 6.4
mg/kg (n=107)

Raludotatug
Deruxtecan
6.4 mg/kg
(n=35)

Raludotatug
Deruxtecan
5.6 mg/kg
(n=36)

Raludotatug
Deruxtecan
4.8 mg/kg
(n=36)

Confirmed ORR, % (95% CI)1

50.5%

(40.6–60.3)

57.1%

(39.4–73.7)

50.0%

(32.9–67.1)

44.4%

(27.9–61.9)

CR, n (%)

3 (2.8%)

0

2 (5.6%)

1 (2.8%)

PR, n (%)

51 (47.7%)

20 (57.1%)

16 (44.4%)

15 (41.7%)

SD, n (%)

42 (39.3%)

10 (28.6%)

15 (41.7%)

17 (47.2%)

PD, n (%)

8 (7.5%)

4 (11.4%)

2 (5.6%)

2 (5.6%)

NE, n (%)

3 (2.8%)

1 (2.9%)2

1 (2.8%)3

1 (2.8%)2

DCR, %

(95% CI)

77.6%

(68.5–85.1)

77.1%

(59.9–89.6)

80.6%

(64.0–91.8)

75.0%

(57.8–87.9)

TTR, weeks, median (range)

7.1 weeks

(5.1–19.1)

7.2 weeks

(5.3–19.1)

6.6 weeks

(5.1–18.3)

7.1 weeks

(5.4–18.7)

Data cutoff: February 26, 2025.

1As accessed by BICR per RECIST 1.1. 2Patient had no baseline tumor assessment by BICR. 3Patient had no adequate post-baseline tumor assessment by BICR.

BICR, blinded independent central review; CR, complete response; DCR, disease control rate; ORR, objective response rate; PD, progressive disease; PR, partial response; RECIST 1.1, Response Evaluation Criteria in Solid Tumors version 1.1; SD, stable disease; TTR, time to response.

About REJOICE-Ovarian01
REJOICE-Ovarian01 is a global, multicenter, randomized, open-label phase 2/3 trial evaluating the efficacy and safety of investigational raludotatug deruxtecan in patients with platinum-resistant, high-grade ovarian, primary peritoneal or fallopian tube cancer, with disease progression following at least one but no more than three prior lines of systemic therapy, including prior treatment with mirvetuximab soravtansine for those with documented high-folate receptor alpha expression. Maintenance therapy (e.g., bevacizumab, poly ADP-ribose polymerase [PARP] inhibitors) is considered part of the preceding line of therapy.

The phase 2 part of REJOICE-Ovarian01 is assessing the safety and tolerability of three doses of raludotatug deruxtecan (4.8 mg/kg, 5.6 mg/kg, or 6.4 mg/kg) to identify the recommended dose for the phase 3 part of the trial. The primary endpoint of the phase 2 part of the trial is ORR as assessed by BICR. Key secondary endpoints include ORR as assessed by investigator, DoR, PFS and DCR – all assessed by both BICR and investigator.

The phase 3 part of REJOICE-Ovarian01 is assessing the efficacy and safety of raludotatug deruxtecan at the selected dose (5.6 mg/kg) compared to investigator’s choice of chemotherapy (paclitaxel, pegylated liposomal doxorubicin, gemcitabine or topotecan). The dual primary endpoints of the phase 3 part of the trial are ORR and PFS as assessed by BICR. Secondary endpoints include PFS and ORR as assessed by investigator, DoR and DCR as assessed by both BICR and investigator, and OS. Pharmacokinetic and biomarker endpoints also will be assessed in both parts of the trial.

REJOICE-Ovarian01 is expected to enroll approximately 710 patients across Asia, Europe, North America, and Oceania. For more information, please visit ClinicalTrials.gov.

About Ovarian Cancer
More than 324,000 women were diagnosed with ovarian cancer worldwide in 2022.4 The median overall survival for advanced ovarian cancer following recurrence can be as little as two years, with a five-year survival rate of 31.8% for those with distant stage disease.1,2

The introduction of targeted therapies has expanded treatment options and improved survival outcomes for some patients with ovarian cancer, but additional options are needed for patients with tumors that progress on available medicines.5 Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens.3 For patients who develop platinum-resistant ovarian cancer, defined as disease progression less than six months after completion of last platinum-based chemotherapy, prognosis is particularly poor and treatment options are limited.6,7

About CDH6
CDH6 (human cadherin-6) is a cadherin family protein overexpressed in several cancers, including ovarian tumors.8 An estimated 65% to 94% of patients with ovarian cancer have tumors that express CDH6.9,10,11 In addition, CDH6 expression is observed more frequently in high-grade serous carcinomas.9, 10,11 There is currently no CDH6 directed medicine approved for treatment of any cancer.

About Raludotatug Deruxtecan
Raludotatug deruxtecan is an investigational, potential first-in-class CDH6 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, raludotatug deruxtecan is comprised of a humanized anti-CDH6 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

(Press release, Merck & Co, OCT 19, 2025, View Source [SID1234656804])