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NCT06819007PHASE3Recruiting

Study of Trastuzumab Deruxtecan With Bevacizumab Versus Bevacizumab Monotherapy for First-line Maintenance in HER2-Expressing Ovarian Cancer (DESTINY-Ovarian01)

Daiichi Sankyo

Start Date

3/19/2025

Completion Date

1/31/2032

Summary

This clinical trial is designed to evaluate the efficacy and safety of T-DXd in combination with bevacizumab versus bevacizumab monotherapy as first-line maintenance therapy, in participants with human epidermal growth factor 2 (HER2)-expressing (immunohistochemistry \[IHC\] 3+/2+/1+) advanced high-grade epithelial ovarian cancer.

Detailed Description

A non-randomized safety run-in phase will be conducted prior to randomization phase to assess the safety of T-DXd in combination with bevacizumab.

Eligibility Criteria

Age Range: 18 years to No maximum

Key Inclusion Criteria: 1. Sign and date the tissue prescreening ICF, prior to HER2 central testing. Sign and date the Main ICF, prior to the start of any trial- specific qualification procedures. Consent to optional PGx prior to any PGx procedures. \*For participants in the safety run-in phase, a safety run-in ICF needs to be signed and dated prior to the start of any trial-specific qualification procedures. 2. Adults ≥18 years of age on the day of signing the ICF. Follow local regulatory requirements if the legal age of consent for trial participation is \>18 years old. 3. Has histologically confirmed diagnosis of epithelial high-grade ovarian, fallopian tube or primary peritoneal carcinoma per local assessment (including but not limiting to serous, endometrioid, clear cell, carcinosarcoma, mucinous). 4. Is newly diagnosed FIGO Stage III or IV. 5. Has HER2 expression per 2016 ASCO-CAP gastric cancer IHC scoring (3+/2+/1+) guidelines1 by prospective central testing. \*For participants in the safety run-in phase, HER2 expression assessed by either local (require using ASCO-CAP gastric cancer IHC scoring \[IHC 3+/2+/1+\] guidelines) or central assessment (if available) is acceptable. Submission of the pathology report is required for participants enrolled based on local HER2 IHC results. 6. Has adequate tumor tissue sample available for assessment of HER2 by central laboratory. Tumor tissue block or sufficient tissue slides are required for HER2 testing and retrospective HRD status determination. \*Participants in the safety run-in phase who are enrolled based on local HER2 IHC results are recommended to provide tumor tissue sample from the same specimen for central assessment. 7. Has a local HRD or BRCA test result available. Participants with BRCA-wildtype will have a local HRD test results, as applicable. 8. Has received up to 6 cycles of standard of care bevacizumab in combination with frontline platinum- based chemotherapy as per approved indication and clinical guidelines and is eligible to continue single agent bevacizumab maintenance per standard of care and investigator discretion. Key Exclusion Criteria: 1. Has ovarian, fallopian tube, or peritoneal cancer of non-epithelial origin. 2. Has a known or suspected deleterious BRCA alteration as per local test that makes the patient eligible for PARP inhibitor. 3. Participant to receive PARP inhibitor as maintenance per standard of care and investigator discretion. Reasons for which the participant is not eligible for PARP inhibitor will be recorded in the eCRF as follows: * HRD negative * HRD positive with SD as best response after platinum * HRD positive non-serous histology Note: For participants enrolled from the Republic of Korea * HRD tested, but inconclusive * HRD positive but safety concern (safety concern to be specified). 4. Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug products and other monoclonal antibodies. 5. Previous Cerebral-Vascular Accident, Transient Ischemic Attack or Sub- Arachnoids Hemorrhage within 6 months prior to randomization. \*Note: For participants enrolled from the Republic of Korea, 6. Has evidence of bleeding diathesis or significant coagulopathy (in the absence of anticoagulation therapy). 7. Has a history of hemorrhagic disorders, abdominal fistula, gastrointestinal perforation, or active gastrointestinal bleeding within 6 months before randomization. 8. Evidence of active or ongoing bowel obstruction. 9. Has a medical history of myocardial infarction within 6 months before randomization, symptomatic congestive heart failure (New York Heart Association Class II to IV). Participants with troponin levels above the upper limit of normal at Screening (as defined by the manufacturer), and without any myocardial infarction related symptoms should have a cardiologic consultation during the Screening Period to rule out myocardial infarction. 10. Has a corrected QT interval prolongation to \>480 msec based on average of the Screening triplicate 12-lead ECG. 11. Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.

Interventions

DRUG

Trastuzumab Deruxtecan

DRUG

Bevacizumab

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Conditions

Ovarian Cancer

Locations

Disney Family Cancer Center

Burbank, California 91505

United States

Scripps Clinic

La Jolla, California 92037

United States

Palo Alto Medical Foundation

Palo Alto, California 94301

United States

Broward Health Medical Center

Fort Lauderdale, Florida 33316

United States

Jupiter Medical Center

Jupiter, Florida 33458

United States

Mount Sinai Medical Center

Miami Beach, Florida 33140

United States

AdventHealth Cancer Institute

Orlando, Florida 32804

United States

Woman's Care FL

St. Petersburg, Florida 33713

United States

Nancy N. & J.C Lewis Cancer & Research Pavillion- St. Josephs/ Candler Health System

Savannah, Georgia 31405

United States

Endeavor Health Evanston Kellogg Cancer Care Center

Evanston, Illinois 60201

United States

Indiana University

Indianapolis, Indiana 46202

United States

Trials365 LLC

Shreveport, Louisiana 71103

United States

Greater Baltimore Medical Center

Towson, Maryland 21204

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02215

United States

Trinity Health St. Joseph Mercy Ann Arbor

Ann Arbor, Michigan 48106

United States

Corewell Health

Grand Rapids, Michigan 49503

United States

Minnesota Oncology Hematology PA

Minneapolis, Minnesota 55404

United States

St. Vincent Gynecologic Oncology

Billings, Montana 59102

United States

Valley Health System

Paramus, New Jersey 07652

United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York 10016

United States

Icahn School of Medicine at Mount Sinai

New York, New York 10029

United States

Columbia University

New York, New York 10032

United States

UNC Hospital

Chapel Hill, North Carolina 27599

United States

Miami Valley Hospital South

Centerville, Ohio 45459

United States

Legacy Medical Group Gynecologic Oncology

Portland, Oregon 97210

United States

Providence Cancer Center Oncology

Portland, Oregon 97213

United States

St. Lukes University Health Network

Bethlehem, Pennsylvania 18015

United States

Ann B Barshinger Cancer Institute

Lancaster, Pennsylvania 17601

United States

Avera Medical Group Gynecologic

Sioux Falls, South Dakota 57105

United States

Sarah Cannon Research Institute (Oncology Associates of Oregon PC)

Nashville, Tennessee 37203

United States

Utah Cancer Specialists Network

Salt Lake City, Utah 84106

United States

Genesiscare St Andrews Hospital

Adelaide,

Australia

Icon Cancer Centre Wesley

Auchenflower,

Australia

Icon Cancer Centre Hobart

Hobart,

Australia

Genesis Care North Shore (Oncology)

St Leonards,

Australia

Westmead Hospital

Sydney,

Australia

Townsville University Hospital Cancer Centre

Townsville, 4814

Australia

Medizinische Universitat Innsbruck

Innsbruck,

Austria

AZ Sint-Lucas

Ghent,

Belgium

UZ Leuven

Leuven,

Belgium

Groupe Sante CHC/Clinique du MontLegia

Liège,

Belgium

CHU UCL Namur

Namur,

Belgium

Cliniques Universitaires Saint-LUC

Woluwe-Saint-Lambert,

Belgium

Oncocentro Belo Horizonte

Belo Horizonte,

Brazil

Centro De Pesquisas Clinica Reichow

Blumenau,

Brazil

Fundação Doutor Amaral Carvalho

Jaú,

Brazil

Liga Norte-Rio-Grandense Contra o Cancer

Natal,

Brazil

Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa Hospital Mae de Deus

Porto Alegre,

Brazil

Irmandade Da Santa Casa De Misericordia De Porto Alegre

Porto Alegre,

Brazil

Ceon Pesquisas

Santo André,

Brazil

Fundacao Faculdade Regional De Medicina De Sao Jose Do Rio Preto

Sao Jose Rio,

Brazil

BP A Beneficencia Portuguesa de Sao Paulo

São Paulo,

Brazil

Complex Oncology Center- Plovdiv EOOD

Plovdiv,

Bulgaria

MHAT Park Hospital EOOD

Plovdiv,

Bulgaria

MHAT Serdika EOOD

Sofia,

Bulgaria

UMHAT Sofiamed EOOD

Sofia,

Bulgaria

UMHAT Tsaritsa Yoanna ISUL EAD

Sofia,

Bulgaria

Ushato Prof Ivan Chernozemski Ead

Sofia,

Bulgaria

Beijing Cancer Hospital

Beijing,

China

The First Hospital of Jilin University

Changchun,

China

Hunan Cancer Hospital

Changsha, 410006

China

Sichuan University West China Second University Hospital

Chengdu,

China

Chongqing Cancer Hospital

Chongqing,

China

The Second Hospital of Dalian Medical University

Dalian,

China

Fujian Cancer Hospital

Fuzhou,

China

Sun Yat-Sen University Cancer Center

Guangzhou,

China

Harbin Medical University - Tumor Hospital

Haerbing,

China

Hainan General Hospital

Haikou,

China

Zhejiang Cancer Hospital

Hangzhou,

China

Women's Hospital School of Medicine Zhejiang University

Hangzhoushi,

China

Shandong Cancer Hospital

Jinan,

China

Yunnan Cancer Hospital

Kunming,

China

Jiangxi Maternal and Child Health Hospital

Nanchang,

China

Zhong Da Hospital, Southeast University

Nanjing,

China

Guangxi Medical University Cancer Hopstial

Nanning,

China

Fudan University Shanghai Cancer Center

Shanghai Shi, 200032

China

Liaoning Cancer Hospital & Institute

Shenyang,

China

Affiliated Hospital (Suzhou First People's Hospital)

Suzhou,

China

Shanxi Cancer Hospital

Taiyuan,

China

Tianjin Medical University Cancer Institute & Hospital

Tianjin,

China

Hubei Cancer Hospital

Wuhan,

China

Tongji Hospital Tongji Medical College of HUST

Wuhan,

China

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an,

China

Yantai Yuhuangding Hospital

Yantai,

China

Henan Cancer Hospital

Zhengzhou,

China

Fakultni Nemocnice Ostrava

Ostrava-Poruba,

Czechia

Fakultni Nemocnice Bulovka

Prague,

Czechia

Fakultni Nemocnice Kralovske Vinohrady

Prague,

Czechia

Fakultni Nemocnice V Motole

Prague,

Czechia

Vseobecna Fakultni Nemocnice V Praze

Prague,

Czechia

Aarhus University Hospital

Aarhus,

Denmark

Rigshospitalet

Copenhagen, 2100

Denmark

Sjællands Universitet Hospital

Roskilde,

Denmark

Institut Bergonie

Bordeaux,

France

Centre Georges Francois Leclerc

Dijon,

France

Hopital Claude Huriez- CHU Lille

Lille,

France

Centre Leon Berard

Lyon,

France

CHU Montpellier, Saint Eloi

Montpellier,

France

Hopital Prive Du Confluent

Nantes,

France

Hopital Saint Joseph- Paris

Paris,

France

Hospital Europeen Georges Pompidou

Paris,

France

CRLCC Eugene Marquis

Rennes,

France

CHU Saint Etienne

Saint-Etienne,

France

Aretaieio Hospital

Athens, 11528

Greece

General Hospital of Athens Alexandra

Athens, 11528

Greece

National And Hapodistrian University of Athens (University General Hospital Attikon)

Athens, 12462

Greece

Metropolitan Hospital

Neo Faliro, 18547

Greece

St Luke's Hospital

Thessaloniki, 55236

Greece

Debreceni Egyetem

Debrecen, 4032

Hungary

Gyor-Moson-Sopron Varmegyei Petz Aladar Egyetemi Oktato Korhaz

Győr, 9024

Hungary

Gujarat Cancer & Research Institute

Ahmedabad,

India

Saroj Gupta Cancer Center and Research Institute SGCC&RI

Kolkata,

India

Tata Memorial Hospital

Mumbai, 400012

India

National Cancer Institute Nagpur

Nagpur,

India

HCG Manavata Cancer Centre

Nashik,

India

Ruby Hall Clinic

Pune,

India

HCG Cancer Centre Vadodara

Vadodara,

India

Mahamana Pandit Madan Mohan Malaviya Cancer Centre

Varanasi, 221005

India

King George Hospital

Visakhapatnam,

India

The Lady Davis Carmel Medical Center

Haifa,

Israel

Shaare Zedek

Jerusalem,

Israel

Meir Medical Center

Kfar Saba,

Israel

Rabin Medical Center-Beilinson Campus

Petah Tikva,

Israel

Tel Aviv Sourasky Medical Center

Tel Aviv,

Israel

Sheba Medical Center

Tel Litwinsky,

Israel

Istituto Tumori Giovanni Paolo II Irccs Ospedale Oncologico Bari

Bari,

Italy

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS

Bologna,

Italy

Azienda Ospedaliera Per Lemergenza Cannizzaro

Catania,

Italy

Humanitas San Pio X

Milan,

Italy

IEO Istituto Europeo Di Oncologia

Milan,

Italy

Azienda Socio Sanitaria Territoriale Di Monza (Presidio San Gerardo)

Monza,

Italy

Istituto Nazionale Tumori Fondazione G. Pascale

Naples,

Italy

Azienda Ospedaliero Universitaria Pisana

Pisa,

Italy

Nuovo Ospedale Degli Infermi

Ponderano,

Italy

Azienda Ospedaliera Universitaria Policlinico Umberto

Roma, 00161

Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma,

Italy

Istituto Nazionale Tumori Regina Elena Irccs

Roma,

Italy

Azienda Ospedaliero Universitaria Citta Della Salute E Della Scienza Di Torino

Torino, 10126

Italy

Hyogo Cancer Center

Akashi, 673-8558

Japan

National Cancer Center Hospital

Chūōku, 104-0045

Japan

Fukushima Medical University Hospital

Fukushima, 960-1295

Japan

Saitama Medical University International Medical Center

Hidaka-Shi, 350-1298

Japan

Cancer Institute Hospital of JFCR

Kōtoku, 135-8550

Japan

Kurume University Hospital

Kurume-shi,

Japan

Aichi Cancer Center Hospital

Nagoya,

Japan

Niigata Cancer Center Hospital

Niigata,

Japan

Okayama University Hosptial

Okayama, 700-8558

Japan

Osaka International Cancer Institute

Osaka,

Japan

Kindai University Hospital

Osakasayama-shi,

Japan

NHO Hokkaido Cancer Center

Sapporo, 003-0804

Japan

Iwate Medical University Hospital

Shiwa-Gun, 028-3695

Japan

Shizuoka Cancer Center

Sunto-gun,

Japan

Mie University Hospital

Tsu, 514-8507

Japan

Yamagata University Hospital

Yamagata, 990-9585

Japan

Hospital Sultan

Johor Bahru,

Malaysia

Sarawak General Hospital

Kuching,

Malaysia

HOSPITAL KUALA LUMPUR(HKL) Kuala

Lumpur,

Malaysia

National Cancer Institute / Institut Kanser Negara

Putrajaya,

Malaysia

Uniwersytecki Szpital Kliniczny w Poznaniu

Poznan, 61848

Poland

Mazowiecki Szpital Wojewodzki W Siedlcach SP Zoo

Siedlce,

Poland

Gral Medical S.R.L

Bucharest,

Romania

Medeuropa SRL

Bucharest,

Romania

Memorial Healthcare International SRL

Bucharest,

Romania

Medeuropa SRL

Oradea,

Romania

National Cancer Centre Singapore

Singapore, 168583

Singapore

National University Hospital

Singapore,

Singapore

Keimyung University Dongsan Hospital

Daegu,

South Korea

National Cancer Center

Goyang-si,

South Korea

CHA Bundang Medical Center, CHA University

Seongnam-si,

South Korea

Seoul National University Bundang Hospital

Seongnam-si,

South Korea

Asan Medical Center

Seoul,

South Korea

Gangnam Severance Hospital, Yonsei University Health System

Seoul,

South Korea

Samsung Medical Center

Seoul,

South Korea

Seoul National University Hospital

Seoul,

South Korea

Severance Hospital, Yonsei University Health System

Seoul,

South Korea

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

Seoul,

South Korea

Complejo Hospitalario Universitario A Coruna

A Coruña,

Spain

Hospital Clinic De Barcelona

Barcelona,

Spain

Hospital Universitari Vall D'Hebron

Barcelona,

Spain

Hospital Universitario Reina Sofia

Córdoba,

Spain

Hospital Universitario Virgen De La Arrixaca

El Palmar,

Spain

Hospital Universitario 12 de Octubre

Madrid,

Spain

Hospital Universitario La Paz

Madrid,

Spain

Hospital Universitario Ramon y Cajal

Madrid,

Spain

Hospital Universitari Son Espases

Palma,

Spain

Clinica Universidad de Navarra (MAD)

Pamplona,

Spain

Hospital Universitario Donostia

Planta Baja,

Spain

Clinica Universidad de Navarra (Calle Marquesado de Santa Marta)

San Blas-Canillejas,

Spain

Hospital Universitario Virgen del Rocio

Seville,

Spain

Hospital Clinico Universitario De Valencia

Valencia,

Spain

Hospital Universitari I Politecnic La Fe

Valencia,

Spain

Skanes Universitetssjukhus Lund

Lund,

Sweden

Karolinska Universitet Ssjukhuset

Solna,

Sweden

Akademiska Sjukhuset (Uppsala University Hospital)

Uppsala, 75185

Sweden

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City,

Taiwan

Chang Gung Memorial Hospital

Linkou Taoyuan,

Taiwan

Taichung Veterans General Hospital

Taichung,

Taiwan

National Cheng Kung University Hospital

Tainan,

Taiwan

MacKay Memorial Hospital- Taipei Branch

Taipei,

Taiwan

National Taiwan University Hospital

Taipei,

Taiwan

Taipei Veterans General Hospital

Taipei,

Taiwan

Addenbrooke's Hospital

Cambridge,

United Kingdom

Guys Hospital Cancer Centre

London, SE1 9RT

United Kingdom

Barts Health NHS Trust

London,

United Kingdom

The Christie Hospital

Manchester,

United Kingdom

Genesis Care, Beaumont House

Oxford, OX4 6LB

United Kingdom

Weston Park Hospital

Sheffield, S10 2SB

United Kingdom