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RecruitingInterventionalPhase 3

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)

NCT ID: NCT06819007Sponsor: Daiichi SankyoLast updated: 2026-05-26

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.

Arms & interventions

  • DrugTrastuzumab Deruxtecan

    T-DXd will be administered at a dose of 5.4 mg/kg intravenously (IV) every 3 weeks (Q3W)

  • DrugBevacizumab

    Bevacizumab will be administered at a dose of 15/mg/kg IV Q3W

Outcome measures

Primary

  • Progression Free Survival by Blinded Independent Central Review (BICR) in the HER2 IHC 3+/2+ population

    Time from randomization to time of objective radiographic disease progression as assessed by BICR based on RECIST v1.1 or death due to any cause.

    Time frame: From date of randomization to radiographic disease progression or death due to any cause, up to approximately 35 months

Secondary

  • Overall Survival in the HER2 IHC 3+/2+ population

    Time frame: From date of randomization to death due to any cause, up to approximately 72 months

  • Progression Free Survival by BICR in the HER2 IHC 3+/2+/1+ population

    Time frame: From date of randomization to radiographic disease progression or death due to any cause, up to approximately 35 months

  • Overall Survival in the HER2 IHC 3+/2+/1+ population

    Time frame: From date of randomization to death due to any cause, up to approximately 72 months

  • Progression Free Survival by the investigator in HER2 IHC 3+/2+ population

    Time frame: From date of randomization to radiographic disease progression or death due to any cause, up to approximately 35 months

  • Progression Free Survival by the investigator in HER2 IHC 3+/2+/1+ population

    Time frame: From date of randomization to radiographic disease progression or death due to any cause, up to approximately 35 months

Eligibility criteria

Sex: FemaleAge: 18 Years and olderHealthy volunteers: No
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 locations (28)

Scripps Clinic

La Jolla, California, 92037

Recruiting

Broward Health Medical Center

Fort Lauderdale, Florida, 33316

Recruiting

Jupiter Medical Center

Jupiter, Florida, 33458

Recruiting

Mount Sinai Medical Center

Miami Beach, Florida, 33140

Recruiting

AdventHealth Cancer Institute

Orlando, Florida, 32804

Recruiting

Woman's Care FL

St. Petersburg, Florida, 33713

Recruiting

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

Savannah, Georgia, 31405

Recruiting

Endeavor Health Evanston Kellogg Cancer Care Center

Evanston, Illinois, 60201

Recruiting

Indiana University

Indianapolis, Indiana, 46202

Recruiting

Trials365 LLC

Shreveport, Louisiana, 71103

Recruiting

Greater Baltimore Medical Center

Towson, Maryland, 21204

Recruiting

Massachusetts General Hospital

Boston, Massachusetts, 02114

Recruiting

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting

Trinity Health St. Joseph Mercy Ann Arbor

Ann Arbor, Michigan, 48106

Recruiting

Corewell Health

Grand Rapids, Michigan, 49503

Recruiting

St. Vincent Gynecologic Oncology

Billings, Montana, 59102

Recruiting

Valley Health System

Paramus, New Jersey, 07652

Recruiting

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016

Recruiting

Icahn School of Medicine at Mount Sinai

New York, New York, 10029

Recruiting

Columbia University

New York, New York, 10032

Recruiting

UNC Hospital

Chapel Hill, North Carolina, 27599

Recruiting

Miami Valley Hospital South

Centerville, Ohio, 45459

Recruiting

Legacy Medical Group Gynecologic Oncology

Portland, Oregon, 97210

Recruiting

Providence Cancer Center Oncology

Portland, Oregon, 97213

Recruiting

St. Lukes University Health Network

Bethlehem, Pennsylvania, 18015

Recruiting

Ann B Barshinger Cancer Institute

Lancaster, Pennsylvania, 17601

Recruiting

Avera Medical Group Gynecologic

Sioux Falls, South Dakota, 57105

Recruiting

Sarah Cannon Research Institute (Oncology Associates of Oregon PC)

Nashville, Tennessee, 37203

Recruiting