A Phase 1b/2 Open-label, Multicenter Study to Evaluate the Safety and Efficacy of Raludotatug Deruxtecan With or Without Other Anticancer Investigational Agents in Participants With High-grade Serous Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Have Relapsed After Prior Platinum-based Chemotherapy
Summary
Researchers are looking for other ways to treat relapsed high-grade serous ovarian cancer. Relapsed means the cancer came back after treatment. High-grade means the cancer cells grow and spread quickly. Serous means the cancer started in the cells that cover the ovaries, the lining of the belly, or in the fallopian tubes. Standard treatment (usual treatment) for people with relapsed high-grade serous ovarian cancer may include: * Chemotherapy, which is a treatment that uses medicine to destroy cancer cells or stop them from growing * Targeted therapy, which is a treatment that works to control how specific types of cancer cells grow and spread Raludotatug deruxtecan (R-DXd) is a study treatment that is an antibody drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. Researchers want to know if R-DXd is safe to take with other treatments and if people tolerate them together. They also want to learn how many people have the cancer respond (gets smaller or goes away) to the treatments.
Detailed description
This study has 2 parts: Part 1 is a dose escalation phase of R-DXd. Part 2 is the expansion phase and will use the Recommended Phase 2 Dose (RP2D) of R-DXd determined in Part 1.
Arms & interventions
- BiologicalRaludotatug Deruxtecan
IV infusion on Day 1 of every 3-week cycle.
- DrugCarboplatin
IV infusion on Day 1 of every 3-week cycle for a maximum of 6 cycles.
- DrugPaclitaxel
IV infusion on Day 1 of every 3-week cycle for a maximum of 6 cycles.
- BiologicalBevacizumab
IV infusion on Day 1 of every 3-week cycle.
- DrugRescue Medication
Includes 5-HT3 Serotonin Receptor Antagonist, NK-1 receptor antagonist, and corticosteroid, administered per protocol.
- BiologicalPembrolizumab
IV infusion on Day 1 of every 3-week cycle for a maximum of 35 cycles.
- DrugGemcitabine
IV injection on days 1 and 8 of each 3-week Cycle
- DrugPegylated liposomal doxorubicin
IV injection administered on Day 1 of each 4-week cycle
Outcome measures
Primary
Part 1: Number of Participants Who Experience a Dose-limiting Toxicity (DLT) Per Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0)
DLTs are defined as toxicities during the DLT evaluation period that are assessed by the investigator to be possibly, probably, or definitely related to study treatment and include: Grade 4 thrombocytopenia of any duration or Grade 3 thrombocytopenia lasting ≥7 days; Grade 3 or higher thrombocytopenia associated with clinically significant bleeding; Grade 4 lymphocytopenia lasting ≥14 days; Grade 4 anemia of any duration; any other Grade 4 hematologic toxicity lasting ≥7 days; febrile neutropenia Grade 3 or Grade 4 meeting pre-specifications; pre-specified hepatic organ toxicities; all Grade 3 or higher other nonhematologic toxicities except those pre-specified; other pre-specified nonhematologic toxicities; any delay in treatment with the planned dose of ≥21 days or discontinuation of treatment due to a toxicity during the DLT evaluation period, or Grade 5 toxicity. The number of participants with DLTs will be reported.
Time frame: Up to 21 days
Part 1: Number of Participants with One or More Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with one or more AEs will be reported.
Time frame: Up to approximately 3 years
Part 1: Number of Participants who Discontinue Study Intervention Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study intervention due to an AE will be reported.
Time frame: Up to approximately 3 years
Part 2: Objective Response Rate (ORR)
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
Time frame: Up to approximately 3 years
Secondary
Part 1: Objective Response Rate (ORR)
Time frame: Up to approximately 3 years
Part 2: Duration of Response (DOR)
Time frame: Up to approximately 3 years
Part 2: Progression-free Survival (PFS)
Time frame: Up to approximately 3 years
Part 2: Overall Survival (OS)
Time frame: Up to approximately 3 years
Part 2: Number of Participants with One or More AEs
Time frame: Up to approximately 3 years
Part 2: Number of Participants who Discontinue Study Intervention Due to an AE
Time frame: Up to approximately 3 years
Eligibility criteria
Study locations (8)
Yale-New Haven Hospital-Smilow Cancer Hospital at Yale-New Haven ( Site 0019)
New Haven, Connecticut, 06510
The University of Louisville, James Graham Brown Cancer Center ( Site 0009)
Louisville, Kentucky, 40202
Dana-Farber Cancer Institute ( Site 0015)
Boston, Massachusetts, 02215
Memorial Sloan Kettering Cancer Center ( Site 0003)
New York, New York, 10065
OU Health University of Oklahoma Medical Center ( Site 7000)
Oklahoma City, Oklahoma, 73104
Houston Methodist Hospital ( Site 0010)
Houston, Texas, 77030
START Mountain Region ( Site 0008)
West Valley City, Utah, 84119
University of Virginia Health System ( Site 0011)
Charlottesville, Virginia, 22908