臨床研究等提出・公開システム

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)

Study of Trastuzumab Deruxtecan with Bevacizumab Versus Bevacizumab Monotherapy for First-line Maintenance in HER2-Expressing Ovarian Cancer (DO-01)

Inoguchi Akihiro

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

dsclinicaltrial_jp@daiichisankyo.com

Contact for Clinical Trial Information

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial_jp@daiichisankyo.com

Recruiting

Mar. 20, 2025

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

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+) guidelines 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.

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.

Female

Ovarian Cancer

Experimental: Treatment Arm A
Participants will receive T-DXd in combination with bevacizumab
T-DXd will be administered at a dose of 5.4 mg/kg intravenously (IV) every 3 weeks (Q3W)
Bevacizumab will be administered at a dose of 15/mg/kg IV Q3W

Active Comparator: Treatment Arm B
Participants will receive bevacizumab monotherapy
Bevacizumab will be administered at a dose of 15/mg/kg IV Q3W

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]

Overall Survival in the HER2 IHC 3+/2+ population
Time interval from the date of randomization to the date of death due to any cause.
[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 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]

Overall Survival in the HER2 IHC 3+/2+/1+ population
Time interval from the date of randomization to the date of death due to any cause.
[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 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.
[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 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.
[Time Frame: From date of randomization to radiographic disease progression or death due to any cause, up to approximately 35 months]

Feb. 13, 2025

Yes

De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/ Supporting Information: - Study Protocol - Statistical Analysis Plan (SAP) - Informed Consent Form (ICF) Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication. Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent. URL: https://vivli.org/ourmember/daiichi-sankyo/

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