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.
This study has 2 parts: Part 1 is a dose escalation phase of R-DXd. Part 2 is the efficacy expansion phase and will use the Recommended Phase 2 Dose (RP2D) of R-DXd determined in Part 1.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
280
IV infusion on Day 1 of every 3-week cycle.
IV infusion on Day 1 of every 3-week cycle for a maximum of 6 cycles.
IV infusion on Day 1 of every 3-week cycle for a maximum of 6 cycles.
IV infusion on Day 1 of every 3-week cycle.
Includes 5-HT3 Serotonin Receptor Antagonist, NK-1 receptor antagonist, and corticosteroid, administered per protocol.
IV infusion on Day 1 of every 3-week cycle for a maximum of 35 cycles.
The University of Louisville, James Graham Brown Cancer Center ( Site 0009)
Louisville, Kentucky, United States
RECRUITINGMemorial Sloan Kettering Cancer Center ( Site 0003)
New York, New York, United States
RECRUITINGHouston Methodist Hospital ( Site 0010)
Houston, Texas, United States
RECRUITINGSTART Mountain Region ( Site 0008)
West Valley City, Utah, United States
RECRUITINGUniversity of Virginia Health System ( Site 0011)
Charlottesville, Virginia, United States
RECRUITINGRambam Health Care Campus ( Site 0202)
Haifa, Israel
RECRUITINGShaare Zedek Medical Center ( Site 0201)
Jerusalem, Israel
RECRUITINGSheba Medical Center ( Site 0200)
Ramat Gan, Israel
RECRUITINGInstitut Català d'Oncologia - L'Hospitalet ( Site 0302)
L'Hospitalet de Llobregat, Barcelona, Spain
RECRUITINGClinica Universidad de Navarra ( Site 0301)
Madrid, Madrid, Comunidad de, Spain
RECRUITING...and 6 more locations
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
Part 1: Objective Response Rate (ORR)
ORR is defined as the percentage of participants who have a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumours version 1.1 (RECIST 1.1). ORR will be assessed by blinded independent central review (BICR).
Time frame: Up to approximately 3 years
Part 2: Duration of Response (DOR)
For participants who demonstrate a confirmed 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), DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by Blinded Independent Central Review (BICR) will be presented.
Time frame: Up to approximately 3 years
Part 2: Progression-free Survival (PFS)
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review (BICR) will be presented.
Time frame: Up to approximately 3 years
Part 2: Overall Survival (OS)
OS is defined as the time from the first dose of study treatment to death due to any cause.
Time frame: Up to approximately 3 years
Part 2: Number of Participants with One or More AEs
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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: 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