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

Phase 3

Recruiting

• Conditions: Ovarian Cancer
• Interventions: Drug: Bevacizumab; Drug: Trastuzumab Deruxtecan

• Registration Number: NCT06819007
• Lead Sponsor: Daiichi Sankyo

Brief 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.

Study Timeline

• Study First Submitted: 2025-02-05
• Study First Submitted QC: 2025-02-05
• Study First Posted: 2025-02-11
• Study Start: 2025-03-19
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-02
• Last Update Posted: 2025-05-06
• Primary Completion: 2028-11-01
• Study Completion: 2032-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 582

Inclusion Criteria

1. Sign and date the tissue prescreening informed consent form (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 (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 breast cancer gene (BRCA) test result available. Participants with BRCA wildtype will have a local HRD test results, as applicable.
8. Has received standard of care bevacizumab in combination with front line 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 BRCA mutation as per local test.
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 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.
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 lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the trial randomization, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, pneumonectomy, etc.)
10. 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.
11. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie pulmonary emboli within three months of the trial enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (ie Rheumatoid arthritis, Sjogren's, sarcoidosis etc.), or prior pneumonectomy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Arm B	Bevacizumab	Participants will receive bevacizumab monotherapy
Treatment Arm A	Trastuzumab Deruxtecan	Participants will receive T-DXd in combination with bevacizumab
Treatment Arm A	Bevacizumab	Participants will receive T-DXd in combination with bevacizumab

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival in the HER2 IHC 3+/2+ population	From date of randomization to death due to any cause, up to approximately 72 months	Time interval from the date of randomization to the date of death due to any cause.
Progression Free Survival by the investigator in HER2 IHC 3+/2+/1+ 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 the investigator based on RECIST v1.1 or death due to any cause.
Progression Free Survival by the investigator in 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 the investigator based on RECIST v1.1 or death due to any cause.
Progression Free Survival by BICR in the HER2 IHC 3+/2+/1+ 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.
Overall Survival in the HER2 IHC 3+/2+/1+ population	From date of randomization to death due to any cause, up to approximately 72 months	Time interval from the date of randomization to the date of death due to any cause.

Trial Locations

Locations (3)

Okayama University Hosptial; 🇯🇵 Okayama, Japan

Hyogo Cancer Center; 🇯🇵 Akashi, Japan

Iwate Medical University Hospital; 🇯🇵 Shiwa-Gun, Japan