A Clinical Study of Raludotatug Deruxtecan in People With Ovarian Cancer (MK-5909-003)

Condition(s) studied

Investigational drug(s) / intervention(s)

Raludotatug Deruxtecan: IV infusion on Day 1 of every 3-week cycle.

Carboplatin: IV infusion on Day 1 of every 3-week cycle for a maximum of 6 cycles.

Paclitaxel: IV infusion on Day 1 of every 3-week cycle for a maximum of 6 cycles.

Bevacizumab: IV infusion on Day 1 of every 3-week cycle.

Rescue Medication: Includes 5-HT3 Serotonin Receptor Antagonist, NK-1 receptor antagonist, and corticosteroid, administered per protocol.

Pembrolizumab: IV infusion on Day 1 of every 3-week cycle for a maximum of 35 cycles.

Gemcitabine: IV injection on days 1 and 8 of each 3-week Cycle

Pegylated liposomal doxorubicin: IV injection administered on Day 1 of each 4-week cycle

MK-2010: IV infusion on Day 1 of every 3-week cycle

Study summary

Researchers are looking for other ways to treat high-grade serous and certain other ovarian cancer. 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 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.

Eligibility

Primary outcome measure(s)

• 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) — Up to 21 days
  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.
• Part 1: Number of Participants with One or More Adverse Events (AEs) — Up to approximately 3 years
  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.
• Part 1: Number of Participants who Discontinue Study Intervention Due to an AE — Up to approximately 3 years
  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.
• Part 2: Objective Response Rate (ORR) — Up to approximately 3 years
  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.
• Part 2: Progression Free Survival (PFS) - Cohort C-2 Arm 1 and Arm 2 — Up to approximately 3 years
  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.

Trial sites (33)