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

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Ovarian Cancer Recurrent

Treatments: Biological: Pembrolizumab; Biological: Bevacizumab; Drug: Rescue Medication; Drug: Paclitaxel; Biological: Raludotatug Deruxtecan; Drug: Carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT06843447

MK-5909-003 (Other Identifier)

REJOICE-Ovarian02 (Other Identifier)

2024-514674-47-00 (Registry Identifier)

U1111-1308-2821 (Registry Identifier)

5909-003

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 280 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has pathologically documented diagnosis of high-grade serous epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
• Has measurable disease per Response Evaluation Criteria In Solid Tumors 1.1
• Participants in Cohort A-1 Arm 2 and Arm 3: Has relapsed disease after 1 to 3 prior lines of therapy and radiographic evidence of disease progression ≥6 months (≥180 days) after the last dose of platinum-based therapy (ie, platinum-sensitive disease).
• Participants in Cohort B-1 and Cohort B-2: Has relapsed disease after 1 to 3 prior lines of therapy and radiographic evidence of disease progression <6 months (<180 days) after the last dose of platinum-based therapy (ie, platinum-resistant disease).
• Participants in Cohort B-1 and Cohort B-2: Is a candidate for bevacizumab treatment
• Has provided tumor tissue from a core or excisional biopsy of a tumor lesion not previously irradiated
• Has an Eastern Cooperative Oncology Group performance status of 0 to 1 assessed within 7 days before allocation
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on anti-retroviral therapy
• Participants who are hepatitis B surface antigen positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to allocation
• Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
• Participants in Cohort C-1 and Cohort D: Has relapsed disease after 1 prior line of therapy, radiographic evidence of disease progression ≥6 months (≥180 days) after the last dose of platinum-based therapy (ie, platinum-sensitive disease) and progressed during prior treatment with PARPi in the first-line setting

Exclusion criteria

• Has any of the following within 6 months before allocation: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event
• Has uncontrolled or significant cardiovascular disease
• Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, and any autoimmune, connective tissue, or inflammatory disorders with potential pulmonary involvement, or prior pneumonectomy
• Has ≥Grade 2 peripheral neuropathy
• Has received prior treatment with cadherin-6-targeted agents
• Has received prior systemic anticancer therapy including investigational agents within 4 weeks or 5 half-lives (whichever is shorter) before allocation
• Has received prior radiotherapy within 2 weeks of the start of study intervention, or has radiation-related toxicities, requiring corticosteroids
• Receives chronic steroid treatment
• Has known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has known active CNS metastases and/or carcinomatous meningitis
• Has history of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD
• Has active infection requiring systemic therapy
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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280 participants in 7 patient groups

Cohort A-1 Arm 1 (R-DXd + Carboplatin Dose 1)

Experimental group

Description:

Participants receive escalating doses of intravenous (IV) raludotatug deruxtecan in combination with carboplatin at Dose 1. Participants can receive up to a maximum of six 3-week cycles of carboplatin (approximately 4 months) and will receive raludotatug deruxtecan until disease progression or discontinuation.

Treatment:

Drug: Carboplatin

Biological: Raludotatug Deruxtecan

Drug: Rescue Medication

Cohort A-1 Arm 2 (R-DXd + Paclitaxel)

Experimental group

Description:

Participants receive escalating doses of IV raludotatug deruxtecan in combination with paclitaxel. Participants can receive up to a maximum of six 3-week cycles of paclitaxel (approximately 4 months) and will receive raludotatug deruxtecan until disease progression or discontinuation.

Treatment:

Biological: Raludotatug Deruxtecan

Drug: Rescue Medication

Drug: Paclitaxel

Cohort A-1 Arm 3 (R-DXd + Carboplatin Dose 2)

Experimental group

Description:

Participants receive escalating doses of intravenous (IV) raludotatug deruxtecan in combination with carboplatin at Dose 2. Participants can receive up to a maximum of six 3-week cycles of carboplatin (approximately 4 months) and will receive raludotatug deruxtecan until disease progression or discontinuation.

Treatment:

Drug: Carboplatin

Biological: Raludotatug Deruxtecan

Drug: Rescue Medication

Cohort B-1 (R-DXd + Bevacizumab)

Experimental group

Description:

Participants receive escalating doses of IV raludotatug deruxtecan in combination with bevacizumab until disease progression or discontinuation.

Treatment:

Biological: Raludotatug Deruxtecan

Drug: Rescue Medication

Biological: Bevacizumab

Cohort B-2 (R-DXd Phase 2 + Bevacizumab)

Experimental group

Description:

Participants with platinum-resistant recurrent ovarian cancer (PRROC) receive recommended Phase 2 dose (RP2D) of IV raludotatug deruxtecan in combination with bevacizumab until disease progression or discontinuation.

Treatment:

Biological: Raludotatug Deruxtecan

Drug: Rescue Medication

Biological: Bevacizumab

Cohort C-1 (R-DXd + Pembrolizumab)

Experimental group

Description:

Participants receive escalating doses of IV raludotatug deruxtecan in combination with pembrolizumab. Participants can receive up to a maximum of thirty-five 3-week cycles of pembrolizumab (approximately 2 years) and will receive raludotatug deruxtecan until disease progression or discontinuation.

Treatment:

Biological: Raludotatug Deruxtecan

Drug: Rescue Medication

Biological: Pembrolizumab

Cohort D (R-DXd Phase 2 +/- Bevacizumab)

Experimental group

Description:

Participants with platinum-sensitive recurrent ovarian cancer (PSROC) receive RP2D of IV raludotatug deruxtecan in combination with or without bevacizumab until disease progression or discontinuation.

Treatment:

Biological: Raludotatug Deruxtecan

Drug: Rescue Medication

Biological: Bevacizumab