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NCT06161025PHASE2, PHASE3Recruiting

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

Daiichi Sankyo

Start Date

2/27/2024

Completion Date

4/30/2030

Summary

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

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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).

Interventions

DRUG

R-DXd

DRUG

Paclitaxel

DRUG

Topotecan

DRUG

PLD

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Conditions

Solid Cancer

Locations

Alaska Women's Cancer Care

Anchorage, Alaska 99508

United States

Yale University School of Medicine

New Haven, Connecticut 06520

United States

Sylvester Comprehensive Cancer Center at Lennar

Coral Gables, Florida 33146

United States

Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida 33442

United States

Florida Cancer Specialists

Lake Mary, Florida 32746

United States

Sylvester Cancer Center

Miami, Florida 33136

United States

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida 33140

United States

Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida 33324

United States

Community MD Anderson Cancer Center- East

Indianapolis, Indiana 46219

United States

Community MD Anderson Cancer Center- South

Indianapolis, Indiana 46227

United States

Community Health Network - MD Anderson

Indianapolis, Indiana 46250

United States

St. Elizabeth Medical Center

Edgewood, Kentucky 41017

United States

Baystate Medical Center

Springfield, Massachusetts 01199-1001

United States

Washington University School of Medicine Obstetrics and Gynecology

St Louis, Missouri 63110

United States

Valley Health System

Paramus, New Jersey 07652

United States

Holy Name

Teaneck, New Jersey 07666

United States

NHPP Imbert

Bay Shore, New York 11706

United States

Northwell Health, LLC PRIME

Lake Success, New York 11042

United States

Perlmutter Cancer Center at NYU Langone Hospital- Long Island

Mineola, New York 11501

United States

NYU Langone Health

New York, New York 10016

United States

NHPP LHH

New York, New York 10065

United States

Duke Women's Cancer Care- Raleigh

Durham, North Carolina 27607

United States

Duke Cancer Center

Durham, North Carolina 27710

United States

Ohio State University Wexner Medical Center

Hilliard, Ohio 43026

United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma 73104

United States

Oklahoma Cancer Specialists and Research Institute

Tulsa, Oklahoma 12967

United States

Oncology Associates of Oregon, P.C.

Eugene, Oregon 97401

United States

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, Pennsylvania 19104-4238

United States

Medical University of South Carolina (MUSC)

Charleston, South Carolina 29425

United States

Sanford Cancer Center Gynecologic Oncology

Sioux Falls, South Dakota 57104

United States

Texas Oncology-Bedford

Bedford, Texas 76022

United States

Houston Area Locations- Woodlands

Conroe, Texas 77384

United States

Texas Oncology-Presbyterian Cancer Center Dallas

Dallas, Texas 75231

United States

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas 75246

United States

Texas Oncology Paris

Fort Worth, Texas 76104

United States

Houston Methodist Hospital

Houston, Texas 77030

United States

University of Texas - MD Anderson

Houston, Texas 77030

United States

Houston Area Locations- Sugar Land

Houston, Texas 77079

United States

Houston Area Locations- West Houston

Houston, Texas 77079

United States

Houston Area Locations- League City

League City, Texas 77573

United States

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia 22903

United States

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington 98109

United States

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin 53226

United States

GenesisCare St Andrews Hospital

Adelaide, 5000

Australia

Peter MacCallum Cancer Center

Melbourne, 3000

Australia

Gold Coast University Hospital

Southport, 4215

Australia

GenesisCare North Shore (Oncology)

St Leonards, 2065

Australia

Oncocentro - Belo Horizonte

Belo Horizonte, 30360680

Brazil

Hospital Ernesto Dornelles

Porto Alegre, 90.160-093

Brazil

Hospital Moinhos de Vento

Porto Alegre, 90035-001

Brazil

Instituto COI de Pesquisa

Rio de Janeiro, 22775-001

Brazil

Arthur J. E. Child Comp CC

Calgary, Alberta T2N 5G2

Canada

London Health Sciences Centre (LHSC) - Victoria Hospital

London, N6A5W9

Canada

McGill University Health Centre/Glen Site / Royal Victoria Hospital

Montreal, H4A 3J1

Canada

The Ottawa Hospital Cancer Centre

Ottawa, K1H 8L6

Canada

University Health Network - Princess Margaret Cancer Centre

Toronto, M5G 2M9

Canada

Beijing Cancer Hospital

Beijing, 100142

China

Chongqing Cancer Hospital

Chongqing, 400030

China

Fujian Provincial Cancer Hospital

Fuzhou, 350015

China

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, 510120

China

Zhejiang Cancer Hospital

Hangzhou, 310022

China

Qilu Hospital of Shandong University

Jinan, 250117

China

Shandong Cancer Hospital

Jinan, 250117

China

Guangxi Medical University Cancer Hospital

Nanning, 530021

China

Fudan University Shanghai Cancer Center

Shanghai, 200032

China

Tianjin Medical University Cancer Institute & Hospital

Tianjin, 453000

China

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, 430022

China

Hubei Cancer Hospital

Wuhan, 430079

China

Fakultni nemocnice Brno

Brno, 625 00

Czechia

Fakultni nemocnice Hradec Kralove

Hradec Králové, 50005

Czechia

Vseobecna fakultni nemocnice v Praze

Prague, 128 08

Czechia

Fakultni nemocnice v Motole

Prague, 150 06

Czechia

Fakultni nemocnice Bulovka

Prague, 180 81

Czechia

Kuopio University Hospital

Kuopio, 70210

Finland

Institut Bergonié

Bordeaux, 33076

France

Centre Francois Baclesse

Caen, 14076

France

Centre Jean Perrin - CLCC

Clermont-Ferrand, 63000

France

Centre Georges François Leclerc

Dijon, 21079

France

Centre Leon Berard

Lyon, 69008

France

Institut Paoli Calmettes

Marseille, 13273

France

Institut du Cancer de Montpellier

Montpellier, 34298

France

Hôpital Privé du Confluent

Nantes, 44277

France

Groupe Hospitalier Diaconesses - Hôpital De La Croix Saint Simon

Paris, 75571

France

CARIO - Centre Armoricain de Radiothérapie, Imagerie médicale et Oncologie

Plérin, 22190

France

Institut Curie

Saint-Cloud, 92210

France

ICL Alexis Vautrin

Vandœuvre-lès-Nancy, 54500

France

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, 01307

Germany

Kliniken Essen-Mitte

Essen, 45136

Germany

Universitaetsklinikum Hamburg-Eppendorf (Ph3)

Hamburg, 20246

Germany

Universitaetsklinikum Mannheim

Mannheim, 68167

Germany

Universitaetsklinikum Ulm

Ulm, 89075

Germany

Aretaieio Hospital

Athens, 11528

Greece

Diagnostic and Therapeutic Centre of Athens "Hygeia" S.A.

Marousi, 15123

Greece

IASO General Clinic

Marousi, 15123

Greece

St Luke's Hospital

Thessaloniki, 55236

Greece

IRCCS Centro di Riferimento Oncologico

Aviano, 33081

Italy

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS

Bologna, 40138

Italy

Azienda Ospedaliera Per Lemergenza Cannizzaro

Catania, 95126

Italy

Azienda Ospedaliera Universitaria Careggi

Florence, 50134

Italy

IEO Istituto Europeo di Oncologia

Milan, 20141

Italy

Humanitas San Pio X

Milan, 20159

Italy

Fondazione IRCCS San Gerardo dei Tintori di Monza

Monza, 20900

Italy

Istituto Nazionale Tumori Fondazione G. Pascale

Naples, 80131

Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168

Italy

Istituto Clinico Humanitas

Rozzano, 20089

Italy

Ospedale Mauriziano Umberto I

Torino, 10128

Italy

Hyogo Cancer Center

Akashi-shi, 673-8558

Japan

National Cancer Center Hospital

Chūōku, 104-0045

Japan

NHO Kyushu Cancer Center

Fukuoka, 811-1395

Japan

Saitama Medical University International Medical Center

Hidaka-shi, 350-1298

Japan

National Cancer Center Hospital East

Kashiwa-shi, 277-8577

Japan

Cancer Institute Hospital of JFCR

Kōtoku, 135-8550

Japan

Jikei University Hospital

Minatoku, 105-8471

Japan

Shizuoka Cancer Center

Nagaizumi-cho, 411-8777

Japan

Aichi Cancer Center Hospital

Nagoya, 464-8681

Japan

Niigata Cancer Center Hospital

Niigata, 951-8566

Japan

Okayama University Hospital

Okayama, 700-8558

Japan

Osaka International Cancer Institute

Osaka, 541-8567

Japan

Hokkaido University Hospital

Sapporo, 060-8648

Japan

Iwate Medical University Hospital

Shiwa-gun, 028-3695

Japan

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, 15-276

Poland

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214

Poland

Uniwersytecki Szpital Kliniczny W Poznaniu

Poznan, 60-569

Poland

Mazowiecki Szpital Wojewodzki w Siedlcach Sp z o o

Siedlce, 08-110

Poland

Hospital Professor Doutor Fernando Fonseca, E.P.E.

Amadora, 2720-276

Portugal

Fundação Champalimaud

Lisbon, 1400-038

Portugal

Hospital da Luz

Lisbon, 1500-650

Portugal

Instituto Português de Oncologia do Porto Francisco Gentil, EPE

Porto, 4200-072

Portugal

National Cancer Center

Goyang-si, 10408

South Korea

Seoul National University Bundang Hospital

Seongnam, 13620

South Korea

CHA Bundang Medical Center, CHA University

Seongnam-si, 13496

South Korea

Seoul National University Hospital

Seoul, 03080

South Korea

Severance Hospital, Yonsei University Health System - Site 8201

Seoul, 03722

South Korea

Severance Hospital, Yonsei University Health System - Site 8207

Seoul, 03722

South Korea

Asan Medical Center

Seoul, 05505

South Korea

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591

South Korea

Samsung Medical Center

Seoul,

South Korea

Hospital Universitari Vall d'Hebron

Barcelona, 08035

Spain

Hospital Clinic de Barcelona

Barcelona, 08036

Spain

ICO Badalona - Hospital Universitari Germans Trias i Pujol

Barcelona, 08916

Spain

Hospital Universitario Ciudad de Jaen

Jaén, 23007

Spain

Hospital Universitario Clinico San Carlos

Madrid, 28040

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Hospital Universitario La Paz

Madrid, 28046

Spain

Clinica Universidad de Navarra (MAD)

Pamplona, 31008

Spain

Clinica Universidad de Navarra

Pamplona, 31008

Spain

Hospital Clínico Universitario Valencia

Valencia, 46010

Spain

Hospital Universitari i Politecnic La Fe

Valencia, 46026

Spain

Taichung Veterans General Hospital

Taichung, 40705

Taiwan

National Cheng Kung University Hospital

Tainan, 70403

Taiwan

National Taiwan University Hospital

Taipei, 100225

Taiwan

Taipei Veterans General Hospital

Taipei, 11217

Taiwan

Koo Foundation Sun Yat-Sen Cancer Center

Taipei, 112

Taiwan

Chang Gung Memorial Hospital,Linkou

Taoyuan City, 333

Taiwan

Baskent University Adana Application and Research Center

Adana, 01240

Turkey (Türkiye)

Cukurova University Medical Faculty

Adana, 01790

Turkey (Türkiye)

Istanbul University Istanbul Medical Faculty

Istanbul, 34093

Turkey (Türkiye)

I. U. Cerrahpasa Faculty of Med

Istanbul, 34153

Turkey (Türkiye)

Medipol University Medical Faculty

Istanbul, 34214

Turkey (Türkiye)

Royal United Hospital

Bath, BA1 3NG

United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN

United Kingdom

Churchill Hospital

Headington, OX3 7LE

United Kingdom

University College London Hospitals

London, NW1 2PG

United Kingdom

Northampton General Hospital (Ph3)

Northampton, NN1 5BD

United Kingdom