Study of Trastuzumab Deruxtecan With Bevacizumab Versus Bevacizumab Monotherapy for First-line Maintenance in HER2-Expressing Ovarian Cancer (DESTINY-Ovarian01)
Trastuzumab Deruxtecan: T-DXd will be administered at a dose of 5.4 mg/kg intravenously (IV) every 3 weeks (Q3W)
Bevacizumab: Bevacizumab will be administered at a dose of 15/mg/kg IV Q3W
Study 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.
Eligibility
Sex
FEMALE
Min age
18 Years
Max age
—
Healthy 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.
Primary outcome measure(s)
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 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.
Trial sites (208)
Facility
City
Region
Status
Disney Family Cancer Center
Burbank
California
Recruiting
Scripps Clinic
La Jolla
California
Recruiting
Palo Alto Medical Foundation
Palo Alto
California
Recruiting
Broward Health Medical Center
Fort Lauderdale
Florida
Recruiting
Jupiter Medical Center
Jupiter
Florida
Recruiting
Mount Sinai Medical Center
Miami Beach
Florida
Recruiting
AdventHealth Cancer Institute
Orlando
Florida
Recruiting
Woman's Care FL
St. Petersburg
Florida
Recruiting
Nancy N. & J.C Lewis Cancer & Research Pavillion- St. Josephs/ Candler Health System
Savannah
Georgia
Recruiting
Endeavor Health Evanston Kellogg Cancer Care Center
Evanston
Illinois
Recruiting
Indiana University
Indianapolis
Indiana
Recruiting
Trials365 LLC
Shreveport
Louisiana
Recruiting
Greater Baltimore Medical Center
Towson
Maryland
Recruiting
Massachusetts General Hospital
Boston
Massachusetts
Recruiting
Dana-Farber Cancer Institute
Boston
Massachusetts
Recruiting
Trinity Health St. Joseph Mercy Ann Arbor
Ann Arbor
Michigan
Recruiting
Corewell Health
Grand Rapids
Michigan
Recruiting
Minnesota Oncology Hematology PA
Minneapolis
Minnesota
Recruiting
St. Vincent Gynecologic Oncology
Billings
Montana
Recruiting
Valley Health System
Paramus
New Jersey
Recruiting
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York
New York
Recruiting
Icahn School of Medicine at Mount Sinai
New York
New York
Recruiting
Columbia University
New York
New York
Recruiting
UNC Hospital
Chapel Hill
North Carolina
Recruiting
Miami Valley Hospital South
Centerville
Ohio
Recruiting
Legacy Medical Group Gynecologic Oncology
Portland
Oregon
Recruiting
Providence Cancer Center Oncology
Portland
Oregon
Recruiting
St. Lukes University Health Network
Bethlehem
Pennsylvania
Recruiting
Ann B Barshinger Cancer Institute
Lancaster
Pennsylvania
Recruiting
Avera Medical Group Gynecologic
Sioux Falls
South Dakota
Recruiting
Sarah Cannon Research Institute (Oncology Associates of Oregon PC)
Nashville
Tennessee
Recruiting
Utah Cancer Specialists Network
Salt Lake City
Utah
Recruiting
Genesiscare St Andrews Hospital
Adelaide
Australia
Recruiting
Icon Cancer Centre Wesley
Auchenflower
Australia
Recruiting
Icon Cancer Centre Hobart
Hobart
Australia
Recruiting
Genesis Care North Shore (Oncology)
St Leonards
Australia
Recruiting
Westmead Hospital
Sydney
Australia
Recruiting
Townsville University Hospital Cancer Centre
Townsville
Australia
Recruiting
Medizinische Universitat Innsbruck
Innsbruck
Austria
Recruiting
AZ Sint-Lucas
Ghent
Belgium
Recruiting
+ 168 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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