Gynecological Cancer
GOG-3112: 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
Description
This is a global, multicenter, open-label, phase 3 trial 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.
Inclusion Notes
For a full description of this trial, please go to the listing on www.clinicaltrials.gov
Participants must meet all of the following criteria to be eligible for enrollment/randomization into the trial:
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.
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.
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).
Is newly diagnosed FIGO Stage III or IV.
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.
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.
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.
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.
Has non-PD after completion of at least 6 cycles and maximum of 8 cycles of front-line carboplatin-paclitaxel (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. In this case, the reason for receiving less than 6 cycles will be recorded in the eCRF.
Non-PD is defined as no evidence of disease (defined as no residual after PDS) or complete response/partial response/stable disease as per 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.
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.
Participants not deemed candidates for surgery or who have completed planned cytoreductive surgery (either PDS or IDS) are eligible.
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 13. Has LVEF ≥50% within 28 days before randomization.
Has urine dipstick for proteinuria < 2+. If urine dipstick is > 2+, 24-hour urine must demonstrate < 1 g of protein in 24 hours.
Has normal blood pressure or adequately treated and controlled hypertension (systolic BP < 140 mmHg and/or diastolic BP < 90 mmHg).
Adequate Organ/Bone Marrow Function
Required within 14 days prior to enrollment/randomization
Transfusion (red blood cell or platelet) or granulocyte colony stimulating factor (G-CSF) administration is not allowed within 14 days prior to screening laboratory tests.
Adequate organ/bone marrow function is defined as:
Has adequate treatment washout period before randomization, defined as:
Female participant of childbearing potential (POCBP), as defined in Section 10.7.1, is eligible to participate if the following conditions are met:
Participant is not pregnant as confirmed by highly sensitive pregnancy test (see Section 10.7.3).
Participant does not breastfeed during the trial intervention period and for at least 7 months after last dose of trial intervention.
Participant agrees to adhere to a contraceptive method that is highly effective (Section 10.7.2) and agrees not to donate eggs (ova, oocytes) to others or freeze/store eggs during the intervention period and for at least the time needed to eliminate each trial intervention after the last dose. The length of time required to continue contraception after last dose for each trial intervention is 7 months. Preservation of eggs may be considered prior to first dose of trial intervention.
Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other trial procedures, and trial restrictions.
Start Date
N/A