Health Condition 1: C569- Malignant neoplasm of unspecifiedovary
Conditions
Interventions
Intervention1: Trastuzumab Deruxtecan: Route: Intravenous
Dose: One IV infusion q3w on Day 1 of each 21 (± 3) day cycle
Duration: Maximum of 34 cycles or until Progression Disease
Control Intervent
Sponsors
Daiichi Sankyo, Inc
Eligibility
Inclusion criteria
Inclusion criteria: Participants must meet all of the following key criteria to be eligible for enrolment/randomization into the trial: 1. Adults greater than equal to 18 years of age on the day of signing the Informed Consent Form. Follow local regulatory requirements if the legal age of consent for trial participation is greater than 18 years old. 2. 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). 3. Is newly diagnosed FIGO Stage III or IV. 4. 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 IHC scoring [IHC 3+/2+/1+] guideline) or central assessment (if available) is acceptable. Submission of the pathology report is required for participants enrolled based on local HER2 IHC results. 5. 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. 6. Has a local HRD or breast cancer gene (BRCA) test result available. Participants with BRCA wildtype will have a local HRD test result, as applicable. 7. Has received standard of care bevacizumab in combination with front line platinumbased chemotherapy as per approved indication and clinical guidelines and is eligible to continue single agent bevacizumab maintenance per standard of care and investigator discretion. 8. Has non-PD after completion of at least 6 cycles and maximum of 8 cycles of front-line carboplatinpaclitaxel (intravenous or intraperitoneal or neoadjuvant/adjuvant chemotherapy or Hyperthermic Intraperitoneal Chemotherapy [HIPEC] is allowed). – Participants with less than 6 cycles of front-line chemotherapy are eligible, only if they had experienced toxicity that precludes additional chemotherapy administration. In this case, the reason for receiving less than 6 cycles will be recorded in the electronic case report form (eCRF). – Non-PD is defined as no evidence of disease (defined as no residual after primary debulking surgery) or complete response/partial response/stable disease as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) assessed by the investigator at the end of front-line chemotherapy. There should be no clinical evidence (physical examination, imagery, or CA 125) of disease progression throughout the participant’s front-line treatment and prior to trial randomization. 9. Trial intervention to start within 3 to 12 weeks of the last dose of front-line chemotherapy. Participants who started bevacizumab maintenance monotherapy before randomization are not eligible. 10. Participants not deemed candidates for surgery or who have completed planned cytoreductive surgery (either primary debulking surgery or interval debulking surgery) are eligible. <b
Exclusion criteria
Exclusion criteria: Participants who meet any of the following key criteria will be disqualified from entering the trial: 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 poly (ADP-ribose) polymerase (PARP) inhibitor as maintenance per standard of care and investigator discretion. Note: Reasons for which the participant is not eligible for PARP inhibitor will be recorded in the electronic case report form (eCRF); 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 a medical history of myocardial infarction within 6 months before randomization, symptomatic congestive heart failure (New York Heart Association Class II to IV2). Participants with troponin levels above the upper limit of normal at Screening (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 greater than 480 msec based on average of the Screening triplicate 12-lead ECG. 11. Has a history of (non-infectious) ILD or pneumonitis that required steroids, has current ILD or pneumonitis, or where suspected ILD or pneumonitis cannot be ruled out by imaging at Screening. 12. 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.) 13. Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the trial. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the trial if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and randomization. 14. Has multiple primary malignancies within 3 years, except adequately resected nonmelanoma skin cancer or curatively treated in-situ disease. 15. Has a history of Nephrotic syndrome
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare the efficacy of T-DXd in combination with bevacizumab (Arm A) versus bevacizumab monotherapy (Arm B) as measured by PFS, as assessed by BICR in the HER2 IHC 3+/2+ population. Endpoint: PFS by BICR in HER2 IHC 3+/2+ population Timepoint: 81 months | — |
Secondary
| Measure | Time frame |
|---|---|
| To compare the efficacy of Arm A versus Arm B as measured by OS in the HER2 IHC 3+/2+ population. Endpoint: OS in HER2 IHC 3+/2+ population Timepoint: 81 months | — |
Countries
Australia, Austria, Belgium, Brazil, Bulgaria, China, Czech Republic, Denmark, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Malaysia, Poland, Republic of Korea, Romania, Singapore, Spain, Sweden, Taiwan, United Kingdom, United States of America
Contacts
Public ContactShweta Pradhan
IQVIA RDS (India) Private Limited
Outcome results
None listed