Clinical trial NCT06819007: Study of Trastuzumab Deruxtecan With Bevacizumab Versus Bevacizumab Monotherapy for First-line Maintenance in HER2-Expressing Ovarian Cancer (DESTINY-Ovarian01)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Ovarian Cancer
Keywords: Ovarian cancer
epithelial ovarian cancer
HER2
Trastuzumab Deruxtecan
Bevacizumab
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2025-02-11
Enrollment: 582
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Key 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.

Primary outcomes:
measure: Progression Free Survival by Blinded Independent Central Review (BICR) in the HER2 IHC 3+/2+ population
timeFrame: From date of randomization to radiographic disease progression or death due to any cause, up to approximately 35 months
Secondary outcomes:
measure: Overall Survival in the HER2 IHC 3+/2+ population
timeFrame: From date of randomization to death due to any cause, up to approximately 72 months
measure: Progression Free Survival by BICR in the HER2 IHC 3+/2+/1+ population
timeFrame: From date of randomization to radiographic disease progression or death due to any cause, up to approximately 35 months
measure: Overall Survival in the HER2 IHC 3+/2+/1+ population
timeFrame: From date of randomization to death due to any cause, up to approximately 72 months
measure: Progression Free Survival by the investigator in HER2 IHC 3+/2+ population
timeFrame: From date of randomization to radiographic disease progression or death due to any cause, up to approximately 35 months
measure: Progression Free Survival by the investigator in HER2 IHC 3+/2+/1+ population
timeFrame: From date of randomization to radiographic disease progression or death due to any cause, up to approximately 35 months
Other outcomes:
Locations:
city: Centerville
country: United States
facility: Miami Valley Hospital South
state: Ohio
city: Shanghai Shi
country: China
facility: Fudan University Shanghai Cancer Center
city: Akashi
country: Japan
facility: Hyogo Cancer Center
city: Chuo-Ku
country: Japan
facility: National Cancer Center Hospital
city: Fukushima-Shi
country: Japan
facility: Fukushima Medical University Hospital
city: Hidaka-Shi
country: Japan
facility: Saitama Medical University International Medical Center
city: Koto-Ku
country: Japan
facility: Cancer Institute Hospital of JFCR
city: Okayama
country: Japan
facility: Okayama University Hosptial
city: Sapporo-Shi
country: Japan
facility: NHO Hokkaido Cancer Center
city: Shiwa-Gun
country: Japan
facility: Iwate Medical University Hospital
city: Tsu-Shi
country: Japan
facility: Mie University Hospital
city: Yamagata-Shi
country: Japan
facility: Yamagata University Hospital
Study officials:
References: