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

NCT06819007 · Daiichi Sankyo
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Official title
A Phase 3, Open-label, Multicenter, Randomized Trial of Trastuzumab Deruxtecan With Bevacizumab Versus Bevacizumab Monotherapy as First-line Maintenance Therapy in HER2-Expressing Ovarian Cancer (DESTINY-Ovarian01/ENGOT-ov89/GEICO144- O/GOG-3112/APGOT-OV13)
About this study
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
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.
Study design
Enrollment target: 582 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-03-19
Estimated completion: 2032-01-31
Last updated: 2026-03-05
Interventions
Drug: Trastuzumab DeruxtecanDrug: Bevacizumab
Primary outcomes
  • Progression Free Survival by Blinded Independent Central Review (BICR) in the HER2 IHC 3+/2+ population (From date of randomization to radiographic disease progression or death due to any cause, up to approximately 35 months)
Sponsor
Daiichi Sankyo · industry
Contacts & investigators
ContactContact for Trial Information · contact · CTRinfo_us@daiichisankyo.com · 908-992-6400
All locations (180)
Scripps ClinicRecruiting
La Jolla, California, United States
Broward Health Medical CenterRecruiting
Fort Lauderdale, Florida, United States
Jupiter Medical CenterRecruiting
Jupiter, Florida, United States
Mount Sinai Medical CenterRecruiting
Miami Beach, Florida, United States
AdventHealth Cancer InstituteRecruiting
Orlando, Florida, United States
Woman's Care FLRecruiting
St. Petersburg, Florida, United States
Nancy N. & J.C Lewis Cancer & Research Pavillion- St. Josephs/ Candler Health SystemRecruiting
Savannah, Georgia, United States
Indiana UniversityRecruiting
Indianapolis, Indiana, United States
Trials365 LLCRecruiting
Shreveport, Louisiana, United States
Greater Baltimore Medical CenterRecruiting
Towson, Maryland, United States
Dana-Farber Cancer InstituteRecruiting
Boston, Massachusetts, United States
Trinity Health St. Joseph Mercy Ann ArborRecruiting
Ann Arbor, Michigan, United States
Corewell HealthRecruiting
Grand Rapids, Michigan, United States
St. Vincent Gynecologic OncologyRecruiting
Billings, Montana, United States
Valley Health SystemRecruiting
Paramus, New Jersey, United States
Laura and Isaac Perlmutter Cancer Center at NYU LangoneRecruiting
New York, New York, United States
Icahn School of Medicine at Mount SinaiRecruiting
New York, New York, United States
UNC HospitalRecruiting
Chapel Hill, North Carolina, United States
Miami Valley Hospital SouthRecruiting
Centerville, Ohio, United States
Legacy Medical Group Gynecologic OncologyRecruiting
Portland, Oregon, United States
Providence Cancer Center OncologyRecruiting
Portland, Oregon, United States
St. Lukes University Health NetworkRecruiting
Bethlehem, Pennsylvania, United States
Ann B Barshinger Cancer InstituteRecruiting
Lancaster, Pennsylvania, United States
Avera Medical Group GynecologicRecruiting
Sioux Falls, South Dakota, United States
Genesiscare St Andrews HospitalRecruiting
Adelaide, Australia
Icon Cancer Centre WesleyRecruiting
Auchenflower, Australia
Icon Cancer Centre HobartRecruiting
Hobart, Australia
Genesis Care North Shore (Oncology)Recruiting
St Leonards, Australia
Westmead HospitalRecruiting
Sydney, Australia
Medizinische Universitat InnsbruckRecruiting
Innsbruck, Austria
AZ Sint-LucasRecruiting
Ghent, Belgium
UZ LeuvenRecruiting
Leuven, Belgium
Groupe Sante CHC/Clinique du MontLegiaRecruiting
Liège, Belgium
CHU UCL NamurRecruiting
Namur, Belgium
Cliniques Universitaires Saint-LUCRecruiting
Woluwe-Saint-Lambert, Belgium
Oncocentro Belo HorizonteRecruiting
Belo Horizonte, Brazil
Centro De Pesquisas Clinica ReichowRecruiting
Blumenau, Brazil
Fundação Doutor Amaral CarvalhoRecruiting
Jaú, Brazil
Liga Norte-Rio-Grandense Contra o CancerRecruiting
Natal, Brazil
Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa Hospital Mae de DeusRecruiting
Porto Alegre, Brazil
Irmandade Da Santa Casa De Misericordia De Porto AlegreRecruiting
Porto Alegre, Brazil
Ceon PesquisasRecruiting
Santo André, Brazil
Fundacao Faculdade Regional De Medicina De Sao Jose Do Rio PretoRecruiting
Sao Jose Rio, Brazil
BP A Beneficencia Portuguesa de Sao PauloRecruiting
São Paulo, Brazil
Complex Oncology Center- Plovdiv EOODRecruiting
Plovdiv, Bulgaria
MHAT Park Hospital EOODRecruiting
Plovdiv, Bulgaria
MHAT Serdika EOODRecruiting
Sofia, Bulgaria
UMHAT Sofiamed EOODRecruiting
Sofia, Bulgaria
UMHAT Tsaritsa Yoanna ISUL EADRecruiting
Sofia, Bulgaria
Ushato Prof Ivan Chernozemski EadRecruiting
Sofia, Bulgaria
Beijing Cancer HospitalRecruiting
Beijing, China
The First Hospital of Jilin UniversityRecruiting
Changchun, China
Sichuan University West China Second University HospitalRecruiting
Chengdu, China
Chongqing Cancer HospitalRecruiting
Chongqing, China
The Second Hospital of Dalian Medical UniversityRecruiting
Dalian, China
Fujian Cancer HospitalRecruiting
Fuzhou, China
Sun Yat-Sen University Cancer CenterRecruiting
Guangzhou, China
Harbin Medical University - Tumor HospitalRecruiting
Haerbing, China
Hainan General HospitalRecruiting
Haikou, China
Zhejiang Cancer HospitalRecruiting
Hangzhou, China
Women's Hospital School of Medicine Zhejiang UniversityRecruiting
Hangzhoushi, China
Shandong Cancer HospitalRecruiting
Jinan, China
Yunnan Cancer HospitalRecruiting
Kunming, China
Jiangxi Maternal and Child Health HospitalRecruiting
Nanchang, China
Zhong Da Hospital, Southeast UniversityRecruiting
Nanjing, China
Guangxi Medical University Cancer HopstialRecruiting
Nanning, China
Fudan University Shanghai Cancer CenterRecruiting
Shanghai Shi, China
Liaoning Cancer Hospital & InstituteRecruiting
Shenyang, China
Affiliated Hospital (Suzhou First People's Hospital)Recruiting
Suzhou, China
Shanxi Cancer HospitalRecruiting
Taiyuan, China
Tianjin Medical University Cancer Institute & HospitalRecruiting
Tianjin, China
Hubei Cancer HospitalRecruiting
Wuhan, China
Tongji Hospital Tongji Medical College of HUSTRecruiting
Wuhan, China
The First Affiliated Hospital of Xi'an Jiaotong UniversityRecruiting
Xi'an, China
Yantai Yuhuangding HospitalRecruiting
Yantai, China
Henan Cancer HospitalRecruiting
Zhengzhou, China
Fakultni Nemocnice OstravaRecruiting
Ostrava-Poruba, Czechia
Fakultni Nemocnice BulovkaRecruiting
Prague, Czechia
Fakultni Nemocnice Kralovske VinohradyRecruiting
Prague, Czechia
Fakultni Nemocnice V MotoleRecruiting
Prague, Czechia
Vseobecna Fakultni Nemocnice V PrazeRecruiting
Prague, Czechia
Aarhus University HospitalRecruiting
Aarhus, Denmark
Sjællands Universitet HospitalRecruiting
Roskilde, Denmark
Institut BergonieRecruiting
Bordeaux, France
Centre Georges Francois LeclercRecruiting
Dijon, France
Hopital Claude Huriez- CHU LilleRecruiting
Lille, France
Centre Leon BerardRecruiting
Lyon, France
CHU Montpellier, Saint EloiRecruiting
Montpellier, France
Hopital Prive Du ConfluentRecruiting
Nantes, France
Hopital Saint Joseph- ParisRecruiting
Paris, France
Hospital Europeen Georges PompidouRecruiting
Paris, France
CRLCC Eugene MarquisRecruiting
Rennes, France
CHU Saint EtienneRecruiting
Saint-Etienne, France
Gujarat Cancer & Research InstituteRecruiting
Ahmedabad, India
Saroj Gupta Cancer Center and Research Institute SGCC&RIRecruiting
Kolkata, India
National Cancer Institute NagpurRecruiting
Nagpur, India
HCG Manavata Cancer CentreRecruiting
Nashik, India
Ruby Hall ClinicRecruiting
Pune, India
HCG Cancer Centre VadodaraRecruiting
Vadodara, India
King George HospitalRecruiting
Visakhapatnam, India
The Lady Davis Carmel Medical CenterRecruiting
Haifa, Israel
Shaare ZedekRecruiting
Jerusalem, Israel
Meir Medical CenterRecruiting
Kfar Saba, Israel
Rabin Medical Center-Beilinson CampusRecruiting
Petah Tikva, Israel
Tel Aviv Sourasky Medical CenterRecruiting
Tel Aviv, Israel
Sheba Medical CenterRecruiting
Tel Litwinsky, Israel
Istituto Tumori Giovanni Paolo II Irccs Ospedale Oncologico BariRecruiting
Bari, Italy
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCSRecruiting
Bologna, Italy
Azienda Ospedaliera Per Lemergenza CannizzaroRecruiting
Catania, Italy
Humanitas San Pio XRecruiting
Milan, Italy
IEO Istituto Europeo Di OncologiaRecruiting
Milan, Italy
Azienda Socio Sanitaria Territoriale Di Monza (Presidio San Gerardo)Recruiting
Monza, Italy
Istituto Nazionale Tumori Fondazione G. PascaleRecruiting
Naples, Italy
Azienda Ospedaliero Universitaria PisanaRecruiting
Pisa, Italy
Nuovo Ospedale Degli InfermiRecruiting
Ponderano, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCSRecruiting
Roma, Italy
Istituto Nazionale Tumori Regina Elena IrccsRecruiting
Roma, Italy
Hyogo Cancer CenterRecruiting
Akashi, Japan
National Cancer Center HospitalRecruiting
Chūōku, Japan
Fukushima Medical University HospitalRecruiting
Fukushima, Japan
Saitama Medical University International Medical CenterRecruiting
Hidaka-Shi, Japan
Cancer Institute Hospital of JFCRRecruiting
Kōtoku, Japan
Kurume University HospitalRecruiting
Kurume-shi, Japan
Aichi Cancer Center HospitalRecruiting
Nagoya, Japan
Niigata Cancer Center HospitalRecruiting
Niigata, Japan
Okayama University HosptialRecruiting
Okayama, Japan
Osaka International Cancer InstituteRecruiting
Osaka, Japan
Kindai University HospitalRecruiting
Osakasayama-shi, Japan
NHO Hokkaido Cancer CenterRecruiting
Sapporo, Japan
Iwate Medical University HospitalRecruiting
Shiwa-Gun, Japan
Shizuoka Cancer CenterRecruiting
Sunto-gun, Japan
Mie University HospitalRecruiting
Tsu, Japan
Yamagata University HospitalRecruiting
Yamagata, Japan
Hospital SultanRecruiting
Johor Bahru, Malaysia
Sarawak General HospitalRecruiting
Kuching, Malaysia
HOSPITAL KUALA LUMPUR(HKL) KualaRecruiting
Lumpur, Malaysia
National Cancer Institute / Institut Kanser NegaraRecruiting
Putrajaya, Malaysia
Mazowiecki Szpital Wojewodzki W Siedlcach SP ZooRecruiting
Siedlce, Poland
Gral Medical S.R.LRecruiting
Bucharest, Romania
Medeuropa SRLRecruiting
Bucharest, Romania
Memorial Healthcare International SRLRecruiting
Bucharest, Romania
Medeuropa SRLRecruiting
Oradea, Romania
National University HospitalRecruiting
Singapore, Singapore
Keimyung University Dongsan HospitalRecruiting
Daegu, South Korea
National Cancer CenterRecruiting
Goyang-si, South Korea
CHA Bundang Medical Center, CHA UniversityRecruiting
Seongnam-si, South Korea
Seoul National University Bundang HospitalRecruiting
Seongnam-si, South Korea
Asan Medical CenterRecruiting
Seoul, South Korea
Gangnam Severance Hospital, Yonsei University Health SystemRecruiting
Seoul, South Korea
Samsung Medical CenterRecruiting
Seoul, South Korea
Seoul National University HospitalRecruiting
Seoul, South Korea
Severance Hospital, Yonsei University Health SystemRecruiting
Seoul, South Korea
The Catholic University of Korea, Seoul St. Mary'S HospitalRecruiting
Seoul, South Korea
Complejo Hospitalario Universitario A CorunaRecruiting
A Coruña, Spain
Hospital Clinic De BarcelonaRecruiting
Barcelona, Spain
Hospital Universitari Vall D'HebronRecruiting
Barcelona, Spain
Hospital Universitario Reina SofiaRecruiting
Córdoba, Spain
Hospital Universitario Virgen De La ArrixacaRecruiting
El Palmar, Spain
Hospital Universitario 12 de OctubreRecruiting
Madrid, Spain
Hospital Universitario La PazRecruiting
Madrid, Spain
Hospital Universitario Ramon y CajalRecruiting
Madrid, Spain
Hospital Universitari Son EspasesRecruiting
Palma, Spain
Clinica Universidad de Navarra (MAD)Recruiting
Pamplona, Spain
Hospital Universitario DonostiaRecruiting
Planta Baja, Spain
Clinica Universidad de Navarra (Calle Marquesado de Santa Marta)Recruiting
San Blas-Canillejas, Spain
Hospital Universitario Virgen del RocioRecruiting
Seville, Spain
Hospital Clinico Universitario De ValenciaRecruiting
Valencia, Spain
Hospital Universitari I Politecnic La FeRecruiting
Valencia, Spain
Skanes Universitetssjukhus LundRecruiting
Lund, Sweden
Karolinska Universitet SsjukhusetRecruiting
Solna, Sweden
Kaohsiung Chang Gung Memorial HospitalRecruiting
Kaohsiung City, Taiwan
Chang Gung Memorial HospitalRecruiting
Linkou Taoyuan, Taiwan
Taichung Veterans General HospitalRecruiting
Taichung, Taiwan
National Cheng Kung University HospitalRecruiting
Tainan, Taiwan
MacKay Memorial Hospital- Taipei BranchRecruiting
Taipei, Taiwan
National Taiwan University HospitalRecruiting
Taipei, Taiwan
Taipei Veterans General HospitalRecruiting
Taipei, Taiwan
Addenbrooke's HospitalRecruiting
Cambridge, United Kingdom
Barts Health NHS TrustRecruiting
London, United Kingdom
The Christie HospitalRecruiting
Manchester, United Kingdom
Study of Trastuzumab Deruxtecan With Bevacizumab Versus Bevacizumab Monotherapy for First-line Maintenance in HER2-Expressing Ovarian Cancer (DESTINY-Ovarian01) · TrialPath