A Phase 3, Multicenter, Randomized, Open-Label Trial of Raludotatug Deruxtecan with or without Bevacizumab as Maintenance Therapy versus Standard of Care in Participants with First Recurrence Platinum-Sensitive, High-Grade Serous or Endometrioid Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (REJOICE-Ovarian03)
A Study of Raludotatug Deruxtecan (R-DXd) with or without Bevacizumab as Maintenance Therapy in Second-Line Platinum-Sensitive Recurrent Ovarian Cancer (REJOICE-Ovarian03)
Inoguchi Akihiro
Daiichi Sankyo Co., Ltd.
1-2-58, Hiromachi, Shinagawa-ku, Tokyo
+81-3-6225-1111
dsclinicaltrial_jp@daiichisankyo.com
Contact for Clinical Trial Information
Daiichi Sankyo Co., Ltd.
1-2-58, Hiromachi, Shinagawa-ku, Tokyo
+81-3-6225-1111
dsclinicaltrial_jp@daiichisankyo.com
Pending
Oct. 01, 2026
600
Interventional
randomized controlled trial
open(masking not used)
active control
parallel assignment
treatment purpose
1. Adult participants with assigned female sex at birth.
2. Participants with histologically or cytologically documented high-grade (Grade 3) serous or endometrioid epithelial ovarian cancer (OVC), primary peritoneal cancer, or fallopian tube cancer.
3. Has an HRD or BRCA test result using a validated or approved test as per applicable regulations available.
4. ECOG PS of 0 or 1.
5. Required baseline local laboratory data (within 7 days prior to randomization) as specified in the protocol.
6. A WOCBP, as specified in the protocol, is eligible to participate if the protocol-specified conditions are met.
7. Must have received 2 prior lines of platinum-based therapy:
- For the first-line (1L) platinum-based chemotherapy (penultimate, platinum-based course prior to enrollment on the trial), must have platinum-sensitive disease after this treatment, defined as documented radiologic disease progression assessed by the investigator (evident measurable or non-measurable disease according to RECIST v1.1) >6 months following the last dose of the platinum administered.
- For the second (last) platinum-based chemotherapy course prior to enrollment on the trial, must have received a platinum-containing regimen for a minimum of 4 cycles and a maximum of 8 cycles.
8. Must have achieved evidence of non-progressive radiological disease based on investigator-assessed RECIST 1.1 and CA-125 at the end of induction treatment with platinum-based doublet chemotherapy (no evidence of disease [NED], complete response [CR], partial response [PR] or stable disease [SD] for participants with measurable disease at baseline; or NED, CR, or non-CR/non-progressive disease [PD] for participants with non-measurable disease based on RECIST v1.1).
9. According to investigator assessment, polymerase inhibitor (PARPi) as 2L maintenance treatment is not the preferred option for the participant.
10. Must be randomized between 4 and 9 weeks after completion of their final dose of the platinum-containing regimen.
11. Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other trial procedures, and trial restrictions.
1. Non-serous or non-endometrioid high-grade epithelial histology, or non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (i.e., germ cell tumors) or low-grade/borderline OVC.
2. Inadequate washout period before randomization, defined as follows:
- Major surgery less than (<)28 days.
- Radiation therapy less than equal to (<=)28 days (if palliative stereotactic radiation therapy without abdominal radiation, <=14 days).
- Systemic anticancer therapy (including but not limited to antibody-drug therapy, retinoid therapy, and hormonal therapy) <28 days or 5 half-lives, whichever is shorter, before starting trial intervention or current participation in other therapeutic investigational procedures.
- Chloroquine/hydroxychloroquine <=14 days.
- Exposure to another investigational trial intervention within 28 days prior to start of trial intervention or current participation in other therapeutic investigational procedures.
3. Clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis, defined as untreated or symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Participants with untreated and asymptomatic brain metastases or participants with previously treated brain metastases who are no longer symptomatic and who require no treatment with steroids may be included in the trial if they have recovered from the acute toxic effect of radiotherapy, at the investigator's discretion. A minimum of 2 weeks must have elapsed between the end of radiotherapy and trial intervention and there should be no evidence of progression or need for steroids treatment or anticonvulsants for at least 2 weeks prior to randomization.
4. Any of the following within the past 6 months prior to randomization: cerebrovascular accident, transient ischemic attack, other arterial thromboembolic event (e.g., intestinal ischemia).
5. Uncontrolled or significant cardiovascular disease.
6. Has any history of ILD/pneumonitis irrespective of steroid use, or current ILD, or suspected ILD, or ILD that cannot be ruled out by imaging at screening. Participants may be eligible if they had history of radiation pneumonitis that did not require steroids. Examples of suspected ILD/pneumonitis by imaging include the presence of lung parenchymal fibrosis, such as CPFE, and any radiographic features consistent with ILA, including but not limited to, extensive ground glass opacities, reticular opacities, traction bronchiectasis, and honeycombing.
7. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within 3 months of the trial enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion, etc.) and any autoimmune, connective tissue, or inflammatory disorders with potential pulmonary involvement (e.g., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior pneumonectomy.
8. Chronic steroid treatment (>10 mg/day prednisone [or equivalent] per day), with the exception of the following:
- Inhaled steroids for asthma or COPD.
- Mineralocorticoids (e.g., fludrocortisone) for participants with orthostatic hypotension.
- Topical steroids for mild skin conditions.
- Low-dose supplemental corticosteroids for adrenocortical insufficiency.
- Premedication for treatment groups and/or premedication in case of any hypersensitivity.
- Intra-articular steroid injections.
9. History of malignancy other than epithelial OVC, primary peritoneal cancer, or fallopian tube cancer within 3 years prior to randomization, with the exception of those with a negligible risk of metastasis or death (e.g., 5-year OS rate >90%) and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, ductal carcinoma in situ, or Stage 1 uterine cancer).
10. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI CTCAE v 6.0, Grade <=1 or baseline.
11. Has current, clinically relevant bowel obstruction (including subocclusive disease) including obstruction related to underlying epithelial OVC, abdominal fistula or gastrointestinal perforation, intra-abdominal abscess.
12. History of severe hypersensitivity (>= Grade 3) or any known contraindication to R-DXd or any excipients in R-DXd.
13. Has active or uncontrolled HIV infection.
14. Has any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses or active infection, substance abuse) or other factors that, in the investigator's opinion, makes it undesirable for the participant to participate in the trial or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required.
15. Has active or uncontrolled HBV infection. Hepatitis B screening testing is required.
16. Has active or uncontrolled HCV infection. Hepatitis C Screening testing is required.
17. Female who is pregnant or breastfeeding or intends to become pregnant during the trial.
18. Psychological, social, familial, or geographical factors that would prevent regular follow-up.
19. Has a history of receiving live-attenuated vaccine (messenger ribonucleic acid [mRNA] and replication-deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to trial intervention.
20. Participants are ineligible if they have a history of any contraindication included in the approved local label for the control group treatment.
Additional Exclusion Criteria for Bevacizumab Participants:
21. Has a history of arterial thromboembolic events, hemorrhage, hemoptysis, active gastrointestinal bleeding that occurred within 6 months before randomization.
22. Participants with history of serious, non-healing wound, active ulcer or untreated bone fracture.
23. History of VEGF therapy related abdominal fistula or gastrointestinal perforation.
24. Participants who discontinued bevacizumab during the second (last) platinum-based chemotherapy due to any AE related to bevacizumab are not eligible to receive bevacizumab.
25. Severe hypersensitivity (>=Grade 3) to bevacizumab and/or any of its excipients. Participants with known sensitivity to Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies are prohibited from receiving bevacizumab during the trial.
26. Participants who have had a major surgical procedure, open biopsy, dental extractions or other dental surgery/procedure that results in an open wound, or significant traumatic injury (e.g., long-bone fracture requiring surgery) as per investigator judgment within 28 days prior to the first date of treatment on this trial, or anticipation of need for major surgical procedure during the course of the trial; participants with placement of vascular access device or core biopsy within 7 days prior to the first date of treatment in the trial.
18age old over
No limit
Female
Fallopian tube cancer
Primary Peritoneal Cancer
High-Grade Serous OVC
Endometrioid Epithelial OVC
Experimental: Arm 1: R-DXd Alone or R-DXd Combined with Bevacizumab
Participants will be randomized to receive either R-DXd, intravenously (IV), every 3 weeks (Q3W) alone, or R-DXd IV along with bevacizumab 15mg/kg, IV, Q3W, on Day 1 of each 21-day cycle, until radiological disease progression according to RECIST v1.1 as assessed by BICR, unacceptable toxicity or other protocol-specified discontinuation criteria are met.
Drug: R-DXd
R-DXd will be administered as an intravenous (IV) infusion.
Drug: Bevacizumab
Bevacizumab will be administered as an IV infusion.
Active Comparator: Arm 2: Bevacizumab Alone or Observation
Participants will be randomized to receive either bevacizumab 15 mg/kg, IV, Q3W, or Investigator's choice of observation until radiological disease progression as assessed by BICR or unacceptable toxicity or until other protocol-specified discontinuation criteria are met.
Drug: Bevacizumab
Bevacizumab will be administered as an IV infusion.
1. Progression Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
PFS is defined as the time (month) from the date of randomization to the earlier date of the first objective documentation of radiographic disease progression as assessed by BICR per RECIST v1.1 or death due to any cause.
[Time Frame: Up to approximately 6 years]
1. Overall Survival (OS)
OS is defined as the time (month) from the date of randomization to the date of death due to any cause.
[Time Frame: Up to approximately 6 years]
2. PFS as Assessed by Investigator per RECIST v1.1
PFS is defined as the time (month) from the date of randomization to the earlier date of the first objective documentation of radiological disease progression as assessed by the investigator per RECIST v1.1 or death due to any cause.
[Time Frame: Up to approximately 6 years]
3. Progression Free Survival 2 (PFS2)
PFS2 is defined as the time (in months) from the date of randomization to the earlier date of the second disease progression, or death due to any cause.
[Time Frame: Up to approximately 6 years]
4. Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE)
TEAEs are defined as those adverse events (AEs) with a start or worsening date during the on-treatment period (from the first dose date to 70 days after the last dose date of study treatment).
[Time Frame: Up to approximately 6 years]
5. Plasma Concentrations of R-DXd (Conjugated Antibody)
[Time Frame: Pre-dose and post-dose at multiple time points during each cycle, up to approximately 6years (Cycle length=21 days)]
6. Plasma Concentrations of Total Anti-Cadherin-6 (CDH6) Antibody
[Time Frame: Pre-dose and post-dose at multiple time points during each cycle, up to approximately 6 years (Cycle length=21 days)]
7. Plasma Concentrations of DXd Payload
[Time Frame: Pre-dose and post-dose at multiple time points during each cycle, up to approximately 6 years (Cycle length=21 days)]
8. Percentage of Participants Having Treatment-Emergent Antidrug Antibody (ADA)
[Time Frame: Pre-dose and post-dose at multiple time points during each cycle, up to approximately 6 years (Cycle length=21 days)]
9. CDH6 Protein Expression in Tumor Tissue as Determined by Immunochemistry Assay (Immunohistochemistry [IHC]) and Correlation with PFS and OS
[Time Frame: Up to approximately 6 years]
10. Change From Baseline in Global Health Status/Quality of Life (QoL) Assessed by European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire Version 3.0 (EORTC QLQ-C30 v3.0)
The EORTC QLQ-C30 assesses 5 functional scales, 3 symptom scales, a global health/QoL scale, and 6 single items. Change in QOL will be assessed using 2 global health/QoL items scored on a 7-point scale ranging from 1 ("very poor") to 7 ("excellent"). Scores are linearly transformed on a scale 0 to 100. A high scale score represents a better QoL.
[Time Frame: Baseline up to approximately 6 years]
11. Change From Baseline in Functional Sub-scales Scores Assessed by EORTC QLQ-C30 v3.0
The EORTC QLQ-C30 assesses 5 functional scales, 3 symptom scales, a global health/QoL scale, and 6 single items. The functional items are scored on a 4-point scale ranging from 1 ("not at all") to 4 ("very much"). Scores are linearly transformed on a scale 0 to 100. A high scale score represents a better functioning.
[Time Frame: Baseline up to approximately 6 years]
12. Change From Baseline in Symptom Sub-scales Score Assessed by EORTC QLQ-C30 v3.0
The EORTC QLQ-C30 assesses 5 functional scales, 3 symptom scales, a global health/QoL scale, and 6 single items. The symptom items are scored on a 4-point scale ranging from 1 ("not at all") to 4 ("very much"). Scores are linearly transformed on a scale 0 to 100. A high scale score represents worst symptoms.
[Time Frame: Baseline up to approximately 6 years]
13. Time to Deterioration (TTD) in Global Health Scale/QoL, Functioning and Symptoms as Measured by EORTC QLQ-C30 v3.0
The EORTC QLQ-C30 assesses 5 functional scales, 3 symptom scales, a global health/QoL scale, and 6 single items. The functional, symptom and single items are scored on a 4-point scale ranging from 1 ("not at all") to 4 ("very much"). The final 2 global health/QoL items are scored on a 7-point scale ranging from 1 ("very poor") to 7 ("excellent"). All of the scales and single-item measures scores are linearly transformed on a scale 0 to 100. A high scale score represents a higher response level and worst symptoms for the symptom scales.
[Time Frame: Up to approximately 6 years]
14. Change From Baseline in Abdominal/Gastrointestinal (GI) Symptoms Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Ovarian Cancer Module (EORTC QLQ-OV28)
The EORTC QLQ-OV28 consists of 28 items assessing abdominal/GI symptoms (6 items), peripheral neuropathy (2 items), other chemotherapy side effects (5 items), hormonal symptoms (2 items), body image (2 items), attitudes to disease/treatment (3 items), sexuality (4 items), indigestion/heartburn (1 item), hair loss (2 items), and change in taste (1 item). All scores range from 0 to 100, with a higher score indicating a worse outcome, except for the sexuality domain, where this is reversed.
[Time Frame: Baseline up to approximately 6 years]
15. Change From Baseline in Attitude to Disease/Treatment Assessed by EORTC QLQ-OV28
The EORTC QLQ-OV28 consists of 28 items assessing abdominal/GI symptoms (6 items), peripheral neuropathy (2 items), other chemotherapy side effects (5 items), hormonal symptoms (2 items), body image (2 items), attitudes to disease/treatment (3 items), sexuality (4 items), indigestion/heartburn (1 item), hair loss (2 items), and change in taste (1 item). All scores range from 0 to 100, with a higher score indicating a worse outcome, except for the sexuality domain, where this is reversed.
[Time Frame: Baseline up to approximately 6 years]
16. TTD in Abdominal/GI Symptoms and Attitude to Disease/Treatment as Measured by EORTC QLQ-OV28
The EORTC QLQ-OV28 consists of 28 items assessing abdominal/GI symptoms (6 items), peripheral neuropathy (2 items), other chemotherapy side effects (5 items), hormonal symptoms (2 items), body image (2 items), attitudes to disease/treatment (3 items), sexuality (4 items), indigestion/heartburn (1 item), hair loss (2 items), and change in taste (1 item). All scores range from 0 to 100, with a higher score indicating a worse outcome, except for the sexuality domain, where this is reversed.
[Time Frame: Up to approximately 6 years]
Daiichi Sankyo Co., Ltd.
Merck Sharp & Dohme LLC
Applicable
Cancer Institute Hospital of JFCR, Institutional Review Board
3-8-31, Ariake, Koto-ku, Tokyo
Approval
July. 08, 2026
Yes
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Supporting Information:
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Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
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