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: Bevacizumab; Drug: MK-2010; Biological: Pembrolizumab; Drug: Paclitaxel; Drug: Pegylated liposomal doxorubicin; Drug: Carboplatin; Biological: Raludotatug Deruxtecan; Drug: Rescue Medication; Drug: Gemcitabine

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 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.

Full 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.

Enrollment: 605 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has pathologically documented diagnosis of high-grade serous or high-grade endometrioid epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
• Participants in Part 1 cohorts and Part 2 Cohort A-2 Arms 1, 2, and 3, Cohort B-2, and Cohort C-2 Arm 3: Has measurable disease per Response Evaluation Criteria In Solid Tumors 1.1
• Participants in Cohort A-1 Arms 2 and 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 must have received no more than 1 prior bevacizumab-containing systemic treatment regimen
• Participants in Cohort B-1, Cohort B-2, Cohort C-2 Arm 3, Cohort E-1 and if administering bevacizumab is planned in Cohort D or Cohort A-2 Arms 1, 2, or 3: Is a candidate for bevacizumab treatment
• Has provided tumor tissue for biomarker research (all cohorts)
• Has an Eastern Cooperative Oncology Group performance status of 0 to 1
• Participants in Cohort C-1, Cohort C-2 Arm 3, Cohort D, and Cohort E-1: 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 poly-ADP ribose polymerase inhibitor (PARPi) in the first-line setting
• Participants in Cohort A-2 Arms 1, 2, and 3: Has relapsed disease after 1 prior line 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 C-2 Arms 1 and 2: Has a new, histologically confirmed diagnosis of International Federation of Gynecology and Obstetrics Stage III or Stage IV epithelial ovarian cancer (high-grade serous or high-grade endometrioid), fallopian tube cancer, or primary peritoneal cancer that is non-homologous recombination deficiency-positive
• Participants in Cohort C-2 Arms 1 and 2: According to the investigator's assessment, PARPi first-line maintenance treatment for non- homologous recombination deficiency (HRD)-positive disease is not the preferred option for the participant
• Participants in Cohort C-2 Arms 1 and 2: According to the investigator's assessment, bevacizumab treatment for non-HRD-positive disease is not the preferred option for the participant

Exclusion criteria

• Has any of the following within 6 months before allocation/randomization: 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 any history of interstitial lung disease (ILD)/pneumonitis irrespective of prior steroid use, current ILD, or suspected ILD, or ILD that cannot be ruled out by imaging at screening
• 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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605 participants in 14 patient groups

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

Experimental group

Description:

Participants receive escalating doses of intravenous (IV) raludotatug deruxtecan (R-DXd) 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: Rescue Medication

Drug: Carboplatin

Biological: Raludotatug Deruxtecan

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

Experimental group

Description:

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

Treatment:

Drug: Rescue Medication

Biological: Raludotatug Deruxtecan

Drug: Paclitaxel

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

Experimental group

Description:

Participants receive escalating doses of intravenous (IV) R-DXd 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 R-DXd until disease progression or discontinuation.

Treatment:

Drug: Rescue Medication

Drug: Carboplatin

Biological: Raludotatug Deruxtecan

Cohort B-1 (R-DXd + Bevacizumab)

Experimental group

Description:

Participants receive escalating doses of IV R-DXd in combination with bevacizumab until disease progression or discontinuation.

Treatment:

Drug: Rescue Medication

Biological: Raludotatug Deruxtecan

Biological: Bevacizumab

Cohort B-2 (R-DXd RP2D + Bevacizumab)

Experimental group

Description:

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

Treatment:

Drug: Rescue Medication

Biological: Raludotatug Deruxtecan

Biological: Bevacizumab

Cohort C-1 (R-DXd + Pembrolizumab)

Experimental group

Description:

Participants receive escalating doses of IV R-DXd 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 R-DXd until disease progression or discontinuation.

Treatment:

Drug: Rescue Medication

Biological: Raludotatug Deruxtecan

Biological: Pembrolizumab

Cohort D (R-DXd +/- Bevacizumab)

Experimental group

Description:

Participants with platinum-sensitive recurrent ovarian cancer (PSROC) receive IV R-DXd in combination with or without bevacizumab until disease progression or discontinuation.

Treatment:

Drug: Rescue Medication

Biological: Raludotatug Deruxtecan

Biological: Bevacizumab

Cohort A-2 Arm 1 (R-DXd RP2D + Carboplatin +/- Bevacizumab)

Experimental group

Description:

Participants with PSROC will receive the RP2D of R-DXd in combination with a maximum of 6 cycles of carboplatin with or without bevacizumab, until disease progression or discontinuation.

Treatment:

Drug: Rescue Medication

Drug: Carboplatin

Biological: Raludotatug Deruxtecan

Biological: Bevacizumab

Cohort A-2 Arm 2 (R-DXd RP2D + Paclitaxel +/- Bevacizumab)

Experimental group

Description:

Participants with PSROC will receive the RP2D of R-DXd in combination with a maximum of 6 cycles of paclitaxel with or without bevacizumab, until disease progression or discontinuation.

Treatment:

Drug: Rescue Medication

Biological: Raludotatug Deruxtecan

Drug: Paclitaxel

Biological: Bevacizumab

Cohort A-2 Arm 3 (Platinum-Based Doublet Chemotherapy +/- Bevacizumab)

Active Comparator group

Description:

Participants with PSROC will receive one of 3 regimens of investigator's choice of platinum-based doublet chemotherapy with or without bevacizumab. Platinum-based doublet chemotherapy will be administered for maximum of 8 cycles. Bevacizumab can be administered until disease progression or discontinuation.

Treatment:

Drug: Gemcitabine

Drug: Carboplatin

Drug: Pegylated liposomal doxorubicin

Drug: Paclitaxel

Biological: Bevacizumab

Cohort E-1 (R-DXd + MK-2010)

Experimental group

Description:

Participants receive escalating doses of IV R-DXd in combination with MK-2010. Participants can receive up to a maximum of thirty-five 3-week cycles of MK-2010 (approximately 2 years) and will receive R-DXd until disease progression or discontinuation.

Treatment:

Drug: Rescue Medication

Biological: Raludotatug Deruxtecan

Drug: MK-2010

Cohort C-2 Arm 1 (Carboplatin + Paclitaxel + Pembrolizumab → R-DXd + Pembrolizumab)

Experimental group

Description:

Participants will receive carboplatin (Dose 1 or Dose 2), paclitaxel (five 3-week cycles), and pembrolizumab during the induction phase. During the maintenance phase, participants will receive RP2D of IV R-DXd (up to 2 years; participants with PR or SD at 2 years may continue until disease progression) in combination with pembrolizumab (up to thirty-five 3-week cycles).

Treatment:

Drug: Carboplatin

Biological: Raludotatug Deruxtecan

Drug: Paclitaxel

Biological: Pembrolizumab

Cohort C-2 Arm 2 (Carboplatin + Paclitaxel)

Experimental group

Description:

Participants will receive carboplatin (Dose 1 or Dose 2) and paclitaxel (seven 3-week cycles), followed by standard of care observation.

Treatment:

Drug: Carboplatin

Drug: Paclitaxel

Cohort C-2 Arm 3 (R-DXd + Pembrolizumab + Bevacizumab)

Experimental group

Description:

Participants with PSROC will receive RP2D of R-DXd in combination with pembrolizumab (up to thirty-five 3-week cycles) and bevacizumab until progressive disease.

Treatment:

Biological: Raludotatug Deruxtecan

Biological: Pembrolizumab

Biological: Bevacizumab