Trastuzumab deruxtecan for Ovarian cancer

Inclusion criteria

• {"criterion_text":"- Sign and date the tissue pre-screening 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.\n- 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.\n- 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).\n- Is newly diagnosed FIGO Stage III or IV.\n- Has HER2 expression per 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 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.\n- 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.\n- 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.\n- 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. Note: Participants should receive up to 6 cycles of bevacizumab in combination with front line platinum-based chemotherapy."}

Exclusion criteria

• {"criterion_text":"- Has ovarian, fallopian tube, or peritoneal cancer of non-epithelial origin.\n- 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.\n- 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.\n- Has a BRCA mutation as per local test.\n- 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).\n- Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug products and other monoclonal antibodies.\n- Previous Cerebral-Vascular Accident, Transient Ischemic Attack or Sub- Arachnoids Hemorrhage within 6 months prior to randomization.\n- Has evidence of bleeding diathesis or significant coagulopathy (in the absence of anticoagulation therapy).\n- Has a history of hemorrhagic disorders, abdominal fistula, gastrointestinal perforation, or active gastrointestinal bleeding within 6 months before randomization.\n- Evidence of active or ongoing bowel obstruction.\n- 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.)."}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"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."}

Secondary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Time interval from the date of randomization to the date of death due to any cause."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Time from randomization to objective radiographic disease progression as assessed by BICR per RECIST v1.1 or death due to any cause."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Time interval from randomization to date of death due to any cause."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Time from randomization to objective radiographic disease progression as assessed by the investigator per RECIST v1.1 or death due to any cause."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Time from randomization to objective radiographic disease progression as assessed by the investigator per RECIST v1.1 or death due to any cause."}

Methods

• Digital Patient Brochure (digital patient-facing brochure to inform potential participants)
• Physician referral letters (Dr-to-Patient letter / Physician Referral Letter to inform treating physicians and encourage referrals)
• Patient Advocacy Group letters (materials to engage patient advocacy groups)
• Social media and clinical trial posts (digital/social media recruitment posts and banner ads)
• Referral Hub content (referral hub materials and pre-screener content for referral workflows)
• Patient Pre-Enrollment Information Card and Patient Wallet Card (printed/digital take-away materials for potential participants)
• Study Information Slides and Talking Points Guide (HCP-targeted study slides and talking points)

Primary sponsor

Full Name

Daiichi Sankyo Europe GmbH

Organisation Type

Pharmaceutical company

Contract research organisations

Name

PPD Development LP

Name

IQVIA Limited

Name

Syneos Health Inc.

Name

Bioclinica Inc.

Responsibilities

ILD Adjudication; Medical Imaging

Name

WCG Clinical Inc.

Responsibilities

Distribution of safety letters to sites and Investigator Brochure to sites

Third parties

• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"ILD Adjudication","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"eCOA/Questionnaires administration","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical Imaging","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"Distribution of safety letters to sites and Investigator Brochure to sites","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"Sponsor e-TMF","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"ctDNA analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Myriad Genetics Inc.","duties_or_roles":"Retrospective testing","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Teckro Limited","duties_or_roles":"Site Engagement Platform","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"IQVIA RDS Hellas Single Member S.A.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}