A Phase 3, Open-label, Multicenter, Randomized Trial of TrastuzumabDeruxtecan with Bevacizumab Versus Bevacizumab Monotherapy asFirst-line Maintenance Therapy in HER2-Expressing Ovarian Cancer.

Investigational Study of Maintenance Therapy in Ovarian Cancer with HER2 Protein

J
Jessica Parker

Primary Investigator

Recruiting
18 years - 100 years
Female
Phase 3
1 participants needed
2 Locations

Brief description of study

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.

Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Detailed description of study

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.

The objective of the HercepTest™ mAb pharmDx (Dako Omnis) use in the non-randomized safety run-in
phase is to select ovarian cancer patients with HER2-expressing (IHC 3+/2+/1+) tumors for enrollment
using HercepTest™ mAb pharmDx (Dako Omnis), if these participants do not have local HER2 IHC test
results. Local HER2 IHC test is out of scope of this Clinical Performance Study Plan (CPSP).
Enrollment of the randomization phase will start when a dosing decision has been made based on the
safety run-in assessment. The objectives of the HercepTest™ mAb pharmDx (Dako Omnis) clinical
performance study in the randomization phase are to:
1) Select ovarian cancer patients with HER2-expressing (IHC 3+/2+/1+) tumors for enrollment using
HercepTest™ mAb pharmDx (Dako Omnis).
2) Stratify patients after enrollment and randomization, based on HER2 status (IHC 1+ vs. 2+ vs. 3+)
using HercepTest™ mAb pharmDx (Dako Omnis).
Only data collected during randomization phase is considered clinical performance study.

The trial (both safety run-in phase and randomization phase) will be divided into 4 periods: Tissue
Prescreening, Screening , Treatment, and Follow-up. HercepTest™ mAb pharmDx (Dako Omnis) will be only
used during tissue prescreening periods in the safety run-in phase (as applicable), and the randomization
phase.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Ovarian cancer
  • Age: 18 years - 100 years
  • Gender: Female

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.

This study investigates the effectiveness of an investigational medication in combination with another medication compared to the other medication alone as a first-line maintenance therapy for patients with HER2-expressing ovarian cancer. HER2 is a protein that can affect the growth of some cancer cells. This study focuses on advanced high-grade epithelial ovarian cancer, which is a type of cancer that begins in the cells on the surface of the ovary.

Participants will first undergo a safety run-in phase to assess the safety of the investigational medication in combination with the other medication. The study is divided into several phases, including tissue prescreening, screening, treatment, and follow-up. During the prescreening phase, a special test will be used to identify patients with HER2-expressing tumors.

  • Who can participate: Adults aged 18 years and older with a confirmed diagnosis of epithelial high-grade ovarian, fallopian tube, or primary peritoneal carcinoma may qualify. Participants must have HER2-expressing tumors and have received standard care with bevacizumab and platinum-based chemotherapy.
  • Study details: Participants will receive either the investigational medication in combination with another medication or the other medication alone. A placebo is not used in this study. Participants will be grouped based on their HER2 status for treatment.
Updated on 25 Nov 2025. Study ID: CTO-GOG-3112, 26342

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