A Study of Raludotatug Deruxtecan (R-DXd) in Subjects With Platinum-resistant, High-grade Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

A Phase 2/3, Multicenter, Randomized Study of Raludotatug Deruxtecan (R-DXd), a CDH6-directed Antibody-drug Conjugate, in Subjects With Platinum-resistant, High-grade Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

This study will evaluate the safety and efficacy of R-DXd therapy in participants with ovarian, peritoneal, or fallopian tube cancer.

Study Overview

• Status: Recruiting
• Conditions: Solid Cancer
• Intervention / Treatment: Drug: R-DXd; Drug: Paclitaxel; Drug: Topotecan; Drug: PLD

Detailed Description

This study will focus on R-DXd in participants with platinum-resistant, high-grade ovarian, primary peritoneal, or fallopian tube cancer. R-DXd is an antibody-drug conjugate that specifically binds to CDH6, which is overexpressed in tumor cells. The Phase 2 dose-optimization part of the study (Part A) intends to define the recommended dose based on safety and efficacy, while the Phase 3 (Part B) part of the study will compare R-DXd with Investigator's choice of chemotherapy and further evaluate efficacy.

• Study Type: Interventional
• Enrollment (Estimated): 860
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Medical Director Contact for Clinical Trial Information; Phone Number: 908-992-6400; Email: CTRinfo_us@daiichisankyo.com

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Recruiting
    • Genesiscare St Andrews Hospital
  • St Leonards, Australia
    • Recruiting
    • GenesisCare North Shore (Oncology)
• Brazil
  • Belo Horizonte, Brazil, 30360680
    • Recruiting
    • Oncocentro - Belo Horizonte
  • Porto Alegre, Brazil, 90035-001
    • Recruiting
    • Hospital Moinhos de Vento
  • Porto Alegre, Brazil, 90.160-093
    • Recruiting
    • Hospital Ernesto Dornelles
  • Rio de Janeiro, Brazil, 22775-001
    • Recruiting
    • Instituto COI de Pesquisa
• Canada
  • Montreal, Canada
    • Recruiting
    • McGill University Health Centre/Glen Site / Royal Victoria Hospital
  • Toronto, Canada
    • Active, not recruiting
    • University Health Network - Princess Margaret Cancer Centre
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Recruiting
      • Arthur J. E. Child Comp CC
• China
  • Beijing, China
    • Active, not recruiting
    • Beijing Cancer Hospital
  • Chongqing, China, 400030
    • Active, not recruiting
    • Chongqing Cancer Hospital
  • Fuzhou, China, 350015
    • Active, not recruiting
    • Fujian provincial Cancer Hospital
  • Guangzhou, China
    • Active, not recruiting
    • The First Affiliated Hospital of Guangzhou Medical University
  • Hangzhou, China, 310022
    • Active, not recruiting
    • Zhejiang Cancer Hospital
  • Jinan, China, 250117
    • Active, not recruiting
    • Shandong Cancer Hospital
  • Jinan, China
    • Active, not recruiting
    • Qilu Hospital of Shandong University
  • Nanning, China
    • Active, not recruiting
    • Guangxi Medical University Cancer Hospital
  • Shanghai, China, 200032
    • Active, not recruiting
    • Fudan University Shanghai Cancer Center
  • Tainan, China
    • Recruiting
    • National Cheng Kung University Hospital
  • Tianjin, China
    • Active, not recruiting
    • Tianjin Medical University Cancer Institute & Hospital
  • Wuhan, China, 430079
    • Active, not recruiting
    • Hubei Cancer Hospital
  • Wuhan, China
    • Active, not recruiting
    • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
• Czechia
  • Brno, Czechia, 625 00
    • Recruiting
    • Fakultni nemocnice Brno
  • Hradec Králové, Czechia, 50005
    • Recruiting
    • Fakultni nemocnice Hradec Kralove
  • Prague, Czechia, 150 06
    • Recruiting
    • Fakultni nemocnice v Motole
  • Prague, Czechia
    • Recruiting
    • Vseobecna fakultni nemocnice v Praze
  • Prague, Czechia
    • Recruiting
    • Fakultni Nemocnice Bulovka
• Finland
  • Kuopio, Finland, 70210
    • Recruiting
    • Kuopio University Hospital
• France
  • Bordeaux, France, 33076
    • Recruiting
    • Institut Bergonié
  • Caen, France, 14076
    • Recruiting
    • Centre François Baclesse
  • Clermont-Ferrand, France, 63000
    • Recruiting
    • Centre Jean Perrin - CLCC
  • Dijon, France, 21079
    • Recruiting
    • Centre Georges Francois Leclerc
  • Lyon, France, 69008
    • Recruiting
    • Centre Léon Bérard
  • Marseille, France, 13273
    • Recruiting
    • Institut Paoli Calmettes
  • Montpellier, France, 34298
    • Recruiting
    • Institut du Cancer de Montpellier
  • Nantes, France, 44277
    • Recruiting
    • Hôpital Privé du Confluent
  • Paris, France, 75571
    • Recruiting
    • Groupe Hospitalier Diaconesses - Hôpital De La Croix Saint Simon
  • Plérin, France, 22190
    • Recruiting
    • CARIO - Centre Armoricain de Radiothérapie, Imagerie médicale et Oncologie
  • Saint-Cloud, France, 92210
    • Recruiting
    • Institut Curie
  • Vandœuvre-lès-Nancy, France, 54500
    • Recruiting
    • ICL Alexis Vautrin
• Germany
  • Dresden, Germany, 01307
    • Recruiting
    • Universitaetsklinikum Carl Gustav Carus TU Dresden
  • Essen, Germany, 45136
    • Recruiting
    • Kliniken Essen-Mitte
  • Mannheim, Germany, 68167
    • Recruiting
    • Universitaetsklinikum Mannheim
  • Ulm, Germany, 89075
    • Recruiting
    • Universitaetsklinikum Ulm
• Greece
  • Marousi, Greece, 15123
    • Recruiting
    • Iaso General Clinic
  • Marousi, Greece, 15123
    • Recruiting
    • Diagnostic and Therapeutic Centre of Athens "Hygeia" S.A.
  • Thessaloniki, Greece, 55236
    • Recruiting
    • St Luke's Hospital
• Italy
  • Aviano, Italy
    • Recruiting
    • IRCCS Centro di Riferimento Oncologico
  • Bologna, Italy, 40138
    • Recruiting
    • Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
  • Catania, Italy
    • Active, not recruiting
    • Azienda Ospedaliera Per Lemergenza Cannizzaro
  • Florence, Italy
    • Recruiting
    • Azienda Ospedaliera Universitaria Careggi
  • Milan, Italy
    • Recruiting
    • IEO Istituto Europeo di Oncologia
  • Milan, Italy
    • Recruiting
    • Humanitas San Pio X
  • Monza, Italy, 20900
    • Recruiting
    • Fondazione IRCCS San Gerardo dei Tintori di Monza
  • Naples, Italy
    • Recruiting
    • Istituto Nazionale Tumori Fondazione G. Pascale
  • Roma, Italy
    • Recruiting
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Rozzano, Italy, 20089
    • Completed
    • Istituto Clinico Humanitas
  • Torino, Italy
    • Recruiting
    • Ospedale Mauriziano Umberto I
• Japan
  • Chūōku, Japan, 104-0045
    • Recruiting
    • National Cancer Center Hospital
  • Fukuoka, Japan, 811-1395
    • Recruiting
    • NHO Kyushu Cancer Center
  • Hidaka-shi, Japan, 350-1298
    • Recruiting
    • Saitama Medical University International Medical Center
  • Kashiwa-shi, Japan, 277-8577
    • Recruiting
    • National Cancer Center Hospital East
  • Kōtoku, Japan, 135-8550
    • Recruiting
    • Cancer Institute Hospital of JFCR
  • Minatoku, Japan, 105-8471
    • Active, not recruiting
    • Jikei University Hospital
  • Nagaizumi-cho, Japan, 411-8777
    • Recruiting
    • Shizuoka Cancer Center
  • Nagoya, Japan, 464-8681
    • Recruiting
    • Aichi Cancer Center Hospital
  • Niigata, Japan, 951-8566
    • Recruiting
    • Niigata Cancer Center Hospital
  • Osaka, Japan, 541-8567
    • Recruiting
    • Osaka International Cancer institute
  • Sapporo, Japan, 060-8648
    • Recruiting
    • Hokkaido University Hospital
  • Shiwa-gun, Japan, 028-3695
    • Recruiting
    • Iwate Medical University Hospital
• Poland
  • Bialystok, Poland, 15-276
    • Recruiting
    • Uniwersytecki Szpital Kliniczny w Bialymstoku
  • Gdansk, Poland
    • Recruiting
    • Uniwersyteckie Centrum Kliniczne
  • Poznan, Poland, 60-569
    • Recruiting
    • Uniwersytecki Szpital Kliniczny w Poznaniu
  • Siedlce, Poland
    • Recruiting
    • Mazowiecki Szpital Wojewodzki w Siedlcach Sp z o o
• Portugal
  • Amadora, Portugal
    • Recruiting
    • Hospital Professor Doutor Fernando Fonseca, E.P.E.
  • Lisbon, Portugal, 1500-650
    • Recruiting
    • Hospital da Luz
• South Korea
  • Goyang-si, South Korea, 10408
    • Recruiting
    • National Cancer Center
  • Seongnam-si, South Korea
    • Recruiting
    • CHA Bundang Medical Center, CHA University
  • Seoul, South Korea
    • Recruiting
    • Samsung Medical Center
  • Seoul, South Korea
    • Recruiting
    • Asan Medical Center
  • Seoul, South Korea
    • Recruiting
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, South Korea, 03080
    • Recruiting
    • National University Hospital
  • Seoul, South Korea, 03722
    • Recruiting
    • Severance Hospital, Yonsei University Health System - Site 8201
  • Seoul, South Korea, 03722
    • Recruiting
    • Severance Hospital, Yonsei University Health System - Site 8207
• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain
    • Recruiting
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08916
    • Recruiting
    • Ico Badalona - Hospital Universitari Germans Trias I Pujol
  • Jaén, Spain
    • Active, not recruiting
    • Hospital Universitario Ciudad de Jaen
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario La Paz
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario Clínico San Carlos
  • Pamplona, Spain
    • Active, not recruiting
    • Clinica Universidad de Navarra
  • Pamplona, Spain
    • Active, not recruiting
    • Clinica Universidad de Navarra (MAD)
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitari i Politècnic La Fe
  • Valencia, Spain
    • Recruiting
    • Hospital Clínico Universitario Valencia
• Taiwan
  • Taichung, Taiwan, 40705
    • Recruiting
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital
  • Taipei, Taiwan
    • Recruiting
    • Koo Foundation Sun Yat-Sen Cancer Center
  • Taoyuan City, Taiwan
    • Recruiting
    • Chang Gung Memorial Hospital,Linkou
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01240
    • Recruiting
    • Baskent University Adana Application and Research Center
  • Istanbul, Turkey (Türkiye), 34153
    • Recruiting
    • I. U. Cerrahpasa Faculty of Med
  • Istanbul, Turkey (Türkiye), 34214
    • Recruiting
    • Medipol University Medical Faculty
• United Kingdom
  • Bath, United Kingdom
    • Active, not recruiting
    • Royal United Hospital
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Recruiting
      • Alaska Women's Cancer Care
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale University School of Medicine
  • Florida
    • Coral Gables, Florida, United States, 33146
      • Active, not recruiting
      • Sylvester Comprehensive Cancer Center at Lennar
    • Deerfield Beach, Florida, United States, 33442
      • Active, not recruiting
      • Sylvester Comprehensive Cancer Center at Deerfield Beach
    • Lake Mary, Florida, United States, 32746
      • Recruiting
      • Florida Cancer Specialists
    • Miami, Florida, United States, 33136
      • Recruiting
      • Sylvester Cancer Center
    • Miami Beach, Florida, United States, 33140
      • Recruiting
      • Mount Sinai Comprehensive Cancer Center
    • Plantation, Florida, United States, 33324
      • Active, not recruiting
      • Sylvester Comprehensive Cancer Center at Plantation
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Recruiting
      • Community Health Network - MD Anderson
    • Indianapolis, Indiana, United States, 46219
      • Active, not recruiting
      • Community MD Anderson Cancer Center- East
    • Indianapolis, Indiana, United States, 46227
      • Active, not recruiting
      • Community MD Anderson Cancer Center- South
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Recruiting
      • St. Elizabeth Medical Center
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199-1001
      • Recruiting
      • Baystate Medical Center
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine Obstetrics and Gynecology
  • New Jersey
    • Paramus, New Jersey, United States, 07652
      • Recruiting
      • Valley Health System
    • Teaneck, New Jersey, United States, 07666
      • Recruiting
      • Holy Name
  • New York
    • Bay Shore, New York, United States, 11706
      • Active, not recruiting
      • NHPP Imbert
    • Lake Success, New York, United States, 11042
      • Recruiting
      • Northwell Health, LLC PRIME
    • Mineola, New York, United States, 11501
      • Active, not recruiting
      • Perlmutter Cancer Center at NYU Langone Hospital- Long Island
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
    • New York, New York, United States, 10065
      • Active, not recruiting
      • NHPP LHH
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Active, not recruiting
      • Duke Cancer Center
    • Durham, North Carolina, United States, 27607
      • Active, not recruiting
      • Duke Women's Cancer Care- Raleigh
  • Ohio
    • Hilliard, Ohio, United States, 43026
      • Recruiting
      • Ohio State University Wexner Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • University of Oklahoma Health Sciences Center
    • Tulsa, Oklahoma, United States, 12967
      • Recruiting
      • Oklahoma Cancer Specialists and Research Institute
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Recruiting
      • Oncology Associates of Oregon, P.C.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-4238
      • Recruiting
      • Perelman School of Medicine at the University of Pennsylvania
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina (MUSC)
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Recruiting
      • Sanford Cancer Center Gynecologic Oncology
  • Texas
    • Bedford, Texas, United States, 76022
      • Active, not recruiting
      • Texas Oncology-Bedford
    • Conroe, Texas, United States, 77384
      • Active, not recruiting
      • Houston Area Locations- Woodlands
    • Dallas, Texas, United States, 75246
      • Active, not recruiting
      • Texas Oncology-Baylor Charles A. Sammons Cancer Center
    • Dallas, Texas, United States, 75231
      • Active, not recruiting
      • Texas Oncology-Presbyterian Cancer Center Dallas
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • Texas Oncology Paris
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas - MD Anderson
    • Houston, Texas, United States, 77079
      • Active, not recruiting
      • Houston Area Locations- Sugar Land
    • Houston, Texas, United States, 77079
      • Active, not recruiting
      • Houston Area Locations- West Houston
    • League City, Texas, United States, 77573
      • Active, not recruiting
      • Houston Area Locations- League City
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • University of Virginia Comprehensive Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • University of Washington - Seattle Cancer Care Alliance
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Froedtert and the Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Sign and date the informed consent form prior to the start of any study-specific qualification procedures.
• Age ≥18 years or the minimum legal adult age (whichever is greater) at the time the informed consent form is signed.
• Participants with histologically or cytologically documented high-grade serous ovarian cancer (OVC), high-grade endometrioid OVC, primary peritoneal cancer, or fallopian tube cancer.
• For Phase 2 (Part A) Participants must have at least 1 lesion, not previously irradiated, amenable to biopsy, and must consent to provide a pretreatment biopsy and on-treatment biopsy tissue sample (on-treatment biopsy sample not required for the Phase 3 part of the study). Fresh pretreatment biopsy may be waived for subjects who consent to provide an archival tumor tissue sample from a lesion not previously irradiated, performed within 6 months of consent and performed after treatment with their most recent cancer therapy regimen.

• For Phase 2 (Part A): Has received at least 1 but no more than 3 prior systemic lines of anticancer therapy. For Phase 3 (Part B): Has received at least 1 but no more than 4 prior systemic lines of anticancer therapy:

  • Neoadjuvant +/-adjuvant considered 1 line of therapy.
  • Maintenance therapy (eg, bevacizumab, poly-ADP ribose polymerase [PARP] inhibitors) will be considered part of the preceding line of therapy.
  • Therapy changed due to toxicity in the absence of progression will be considered part of the same line.
  • Hormonal therapy will be counted as a separate line of therapy, unless it was given as maintenance.
  • At least 1 line of therapy containing bevacizumab, unless the subject is not eligible for treatment with bevacizumab due to precautions/intolerance. Note: Subjects must have progressed radiologically on or after their most recent line of systemic therapy. Biochemical progression will not be considered progression for this study.
• Has platinum-resistant disease. If a subject had only 1 line of platinum therapy, must have received at least 4 cycles of platinum, must have had a best response of not PD, and then progressed between >90 and ≤180 days after the date of the last dose of platinum If a subject had 2 or 4 lines of platinum therapy, must have received at least 2 cycles of platinum and have progressed on or within 180 days after the date of the last dose of platinum.
• If mirvetuximab soravtansine (MIRV) is locally available: Has had prior treatment with MIRV for participants with documented high-folate receptor alpha expression, unless the participant is not eligible for treatment with mirvetuximab soravtansine due to precautions/intolerance, or if the treatment is not approved or available locally.
• Has at least 1 measurable lesion evaluated by computed tomography or magnetic resonance imaging according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) per investigator assessment.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Has adequate organ and bone marrow function as assessed by local laboratory (within 14 days before start of study drug administration).
• Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures and study restrictions.
• For Phase 3 (Part B) only: Subjects must be eligible for one of the treatments included in the investigator's choice of chemotherapy arm.

Exclusion Criteria

• Has clear cell, mucinous, or sarcomatous histology, mixed tumors containing any histology, or low-grade/borderline OVC. (Note for Phase 3 [Part B]: seromucinous, low-grade serous carcinoma or ovarian sarcoma, carcinosarcoma and undifferentiated carcinoma are excluded.)

• Inadequate washout period before Cycle 1 Day 1, defined as follows:

  • Major surgery <28 days
  • Radiation therapy <28 days (if palliative stereotactic radiation therapy without abdominal radiation, ≤14 days)
  • Systemic anticancer therapy (including antibody-drug therapy, retinoid therapy, and hormonal therapy) <28 days or 5 half-lives, whichever is shorter, before starting study drug
  • Chloroquine/hydroxychloroquine <14 days
  • Exposure to another investigational drug within 28 days prior to start of study treatment or current participation in other therapeutic investigational procedures
• 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. Subjects with untreated and asymptomatic brain metastases or subjects with treated brain metastases who are no longer symptomatic and who require no treatment with steroids may be included in the study 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 randomization and there should be no evidence of progression or need for steroid treatment or anticonvulsants for at least 2 weeks prior to randomization. Note: If there is a history or suspicion of central nervous system. Note: If there is a history or suspicion of central nervous system metastasis, a CT scan of the head or MRI of the brain must be performed at baseline.
• Any of the following within the past 6 months prior to randomization: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event.

• Uncontrolled or significant cardiovascular disease, including the following:

  • QT interval corrected with Fridericia's formula interval >470 ms.
  • Diagnosed or suspected long QT syndrome.
  • History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes.
  • The participant has bradycardia of less than 50 bpm, unless the subject has a pacemaker.
  • History of second- or third-degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers and have no history of fainting or clinically relevant arrhythmia with pacemakers.
  • Myocardial infarction within 6 months prior to screening.
  • Uncontrolled angina pectoris within 6 months prior to screening.
  • New York Heart Association Class 3 or 4 congestive heart failure.
  • Left ventricular ejection fraction <50% or institutional lower limit of normal as measured by echocardiography or multigated acquisition (MUGA) scan.
  • Coronary/peripheral artery bypass graft within 6 months prior to screening
  • Uncontrolled hypertension (HgCTCAE Grade ≥3 hypertension as per NCI-CTCAE version 5.0).
  • Complete left or right bundle branch block.
• Has a history of (noninfectious) ILD/pneumonitis that required corticosteroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion, etc) and any autoimmune, connective tissue, or inflammatory disorders with potential pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc), or prior pneumonectomy.

• Chronic steroid treatment (>10 mg/day), with the exception of the following:

  • Inhaled steroids for asthma or COPD
  • Mineralocorticoids (eg, fludrocortisone) for subjects 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
• History of malignancy other than epithelial OVC, primary peritoneal cancer, or fallopian tube cancer within 3 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death (eg, 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).

• Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE Version 5.0, Grade ≤1 or baseline. Note: Subjects may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to Grade >2 for 3 months prior to randomization and managed with SOC treatment) that the investigator deems related to previous anticancer therapy, following discussion with the Sponsor, such as the following:

  • Chemotherapy-induced neuropathy
  • Fatigue
  • Endocrinopathies, which may include hypothyroidism, hyperthyroidism, Type 1 diabetes, hyperglycemia, and adrenal insufficiency
  • Skin pigmentation (vitiligo)
• For Phase 2 (Part A): Prior exposure to other CDH6-targeted agents or an ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan or datopotamab deruxtecan). For Phase 3 (Part B): Prior exposure to other CDH6-targeted agents or an antibody-drug conjugate containing a topoisomerase I inhibitor.
• History of hypersensitivity to any excipients in the R-DXd or any known contraindication to treatment with, including hypersensitivity to, the study drug(s).
• Has an active or uncontrolled human immunodeficiency virus (HIV) infection.
• 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 subject to participate in the study or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required.
• Has an active or uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Hepatitis B and Hepatitis C Screening tests are required.

Subjects are eligible if:

1. Hepatitis B virus surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization.
2. History of hepatitis C infection: eligible if the HCV viral load is below the level of detection in the absence of antiviral therapy during the previous 4 weeks.

3. Have normal transaminase values, or, if liver metastases are present, abnormal transaminases with a result of AST/ALT <3 × ULN, which are not attributable to HCV infection.

   • Female who is pregnant or breastfeeding or intends to become pregnant during the study.
   • Psychological, social, familial, or geographical factors that would prevent regular follow-up.
   • Prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the subject; alter the absorption, distribution, metabolism, or excretion of the study drug; or confound the assessment of study results.
   • Has a history of receiving live-attenuated vaccine (messenger RNA [mRNA] and replication-deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to study intervention.
   • For Phase 3 (Part B) only: Has clinical symptoms or radiographic evidence of intestinal obstruction.
   • For Phase 3 (Part B) only: Has ascites or pleural effusions that require repeated drainage (less than 4 weeks between drainages).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: R-DXd 4.8mg/kg Q3W; Participants will be randomized to receive intravenous R-DXd administered at a dose of 4.8 mg/kg every 3 weeks (Q3W).	Drug: R-DXd; R-DXd will be administered as an intravenously (IV) infusion; Other Names: DS-6000a
Experimental: Part A: R-DXd 5.6 mg/kg Q3W; Participants will be randomized to receive intravenous R-DXd administered at a dose of 5.6 mg/kg every 3 weeks (Q3W).	Drug: R-DXd; R-DXd will be administered as an intravenously (IV) infusion; Other Names: DS-6000a
Experimental: Part A: R-DXd 6.4 mg/kg Q3W; Participants will be randomized to receive intravenous R-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).	Drug: R-DXd; R-DXd will be administered as an intravenously (IV) infusion; Other Names: DS-6000a
Experimental: Part B: R-DXd RP3D Q3W; Participants will be randomized to receive intravenous R-DXd administered at the Recommended Phase 3 Dose (RP3D) every 3 weeks (Q3W).	Drug: R-DXd; R-DXd will be administered as an intravenously (IV) infusion; Other Names: DS-6000a
Active Comparator: Part B: Investigator's Choice; Participants will be randomized to receive intravenous treatment with investigator's choice of paclitaxel, pegylated liposomal doxorubicin (PLD), or topotecan.	Drug: Paclitaxel; Paclitaxel will be administered as an IV infusion; Drug: Topotecan; Topotecan will be administered as an IV infusion; Drug: PLD; PLD will be administered as an IV infusion; Other Names: Pegylated Liposomal Doxorubicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) Assessment (Part A)	The ORR was defined as the percentage of participants with confirmed Complete Response (CR) or Partial Response (PR), by BICR assessment based on RECIST version 1.1.	From date of randomization to data cut off, up to 18 months
Progression-free Survival (PFS) Based on BICR Assessment (Part B)	PFS is defined as the time from the date of randomization to the date of disease progression, defined as the first documented radiological progression or death due to any cause, whichever comes first.	From date of randomization to data cut off, up to 26 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	DoR is defined as the time from the date of the first documentation of objective tumor response (CR or PR) that is subsequently confirmed to the first documentation of disease progression or death due to any cause, whichever occurs first.	From date of randomization to data cut off, up to 40 months
Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of death due to any cause.	From date of randomization to data cut off, up to 40 months
Number of participants with Treatment-emergent Adverse Events (TEAEs)	TEAEs are defined as those AEs with a start or worsening date during the on-treatment period (from the first dose date to 40 days after the last dose date of study treatment).	From first dose to data cut off, up to 40 months
Pharmacokinetic (PK) Analysis: Maximum Plasma Drug Concentration (Cmax) of R-DXd		From first dose to data cut off, up to 40 months
Pharmacokinetic (PK) Analysis: Time to Reach Maximum Plasma Drug Concentration (Tmax) of R-DXP		From first dose to data cut off, up to 40 months
Pharmacokinetic (PK) Analysis: Area Under the Concentration-Time Curve (AUC) of R-DXd		From first dose to data cut off, up to 40 months
Pharmacokinetic (PK) Analysis: Terminal Half-Life (t1/2) of R-DXd		From first dose to data cut off, up to 40 months
Percentage of Participants With Treatment Emergent Antidrug Antibody (ADA)		From baseline to data cut off, up to 40 months
Percentage of Participants With Cancer Antigen 125 (CA-125) Response Rate	CA-125 response rate is defined as the percentage of participants with a reduction of 50% in CA-125 levels when compared to levels from a pretreatment sample, as assessed by blood sample based on Gynecological Cancer InterGroup criteria	From baseline to data cut off, up to 40 months
Time to Next Treatment (TTNT)	TTNT is defined as the time from randomization to the start date of the next line of therapy	From date of randomization to data cut off, up to 40 months
Cadherin-6 (CDH6) protein expression in tumor tissue as determined by immunochemistry assay and correlation with ORR, DoR, PFS and OS	CDH6 protein expression in tumor tissue as determined by immunohistochemistry.	From baseline to data cut off, up to 40 months
Objective Response Rate (ORR) Based on Investigator Assessment	The ORR was defined as the percentage of participants who achieved Best Overall Response (BOR) of confirmed Complete Response (CR) or Partial Response (PR), by Investigator assessment based on RECIST version 1.1.	From date of randomization to data cut off, up to 30 months
Progression-free Survival (PFS) Based on BICR and Investigator Assessment	PFS is defined as the time from the date of randomization to the date of disease progression, defined as the first documented radiological progression or death due to any cause.	From date of randomization to data cut off, up to 30 months
Disease Control Rate (DCR)	DCR is defined as the proportion of participants who achieved a confirmed CR, PR, or stable disease maintained for ≥12 weeks, as assessed by BICR and investigator based on RECIST version 1.1	From date of randomization to data cut off, up to 40 months
Progression-free Survival 2 (PFS2) Based on Investigator Assessment	PFS2 is defined as the time from randomization to the first documented objective disease progression on next line therapy or death due to any cause, whichever comes first.	From date of randomization to data cut off, up to 40 months
Change from Baseline in Abdominal/gastrointestinal (GI) Symptoms (Part B)	Change from baseline in abdominal and gastrointestinal symptoms as measured by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) OV28 abdominal/GI subscale	From baseline to Week 12 and up to data cut off, up to 40 months
Change from Baseline in Fatigue/Pain Symptoms (Part B)	Change from baseline as measured by the EORTC QLQ C30 Fatigue/Pain subscale score	From baseline to data cut off, up to 40 months
Time to Deterioration in Fatigue/Pain Symptoms (Part B)	Time to deterioration in pain from baseline as measured by the EORTC QLQ C30 Fatigue/Pain subscale score	From baseline to data cut off, up to 40 months
Time to Deterioration in GI Symptoms (Part B)	Time to deterioration in pain from baseline as measured by the EORTC QLQ OV28 abdominal/GI subscale total score	From baseline to data cut off, up to 40 months
Time to Deterioration in Disease Impacts (Part B)	Time to deterioration in selected subscales of EORTC QLQ C30; physical functioning, global health status, overall quality of life.	From baseline to data cut off, up to 40 months
Change from Baseline in Disease Impacts (Part B)	Change from Baseline in selected subscales of EORTC QLQ C30; physical functioning, global health status, overall quality of life.	From baseline to data cut off, up to 40 months

Collaborators and Investigators

• Sponsor: Daiichi Sankyo
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Global Clinical Leader, Daiichi Sankyo

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2024
• Primary Completion (Estimated): February 29, 2028
• Study Completion (Estimated): April 30, 2030

Study Registration Dates

• First Submitted: November 27, 2023
• First Submitted That Met QC Criteria: December 6, 2023
• First Posted (Actual): December 7, 2023

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Ovarian cancer; Fallopian tube cancer; Primary pertioneal cancer; Raludotatug Deruxtecan (R-DXd); Cadherin 6 (CDH6)
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Fallopian Tube Diseases; Ovarian Neoplasms; Fallopian Tube Neoplasms; Organic Chemicals; Heterocyclic Compounds; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Camptothecin; Alkaloids; Taxoids; Cyclodecanes; Diterpenes; Paclitaxel; Topotecan; liposomal doxorubicin; 1-dodecylpyridoxal
• Other Study ID Numbers: DS6000-109; REJOICE-Ovarian01 (Other Identifier: Daiichi Sankyo); ENGOT-ov77 (Other Identifier: ENGOT); GOG-3096 (Other Identifier: GOG); jRCT2031230556 (Other Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No