RecruitingNCT06843447ClinicalTrials.gov record

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

Ovarian Cancer Recurrent

Ask WCR about this study Official registry record ↗

THE QUICK READ

What this study involves

The registry says this study is recruiting. Individual locations may have different availability.

Study type: Interventional
Phase: Phase 1 / Phase 2
Age range: 18 years - Not specified
Sex eligible: Female
Healthy volunteers: Not accepted
Participants: 605 Estimated

These are starting points, not an eligibility decision. The research team must review the full requirements.

About the research

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.

Read the 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.

Who may be able to participate?

The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.

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

Understand screening

Treatment, groups and participation

The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.

Assignment: Not randomized
Masking: No masking

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

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.

Biological: Raludotatug Deruxtecan · Drug: Carboplatin · Drug: Rescue Medication

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

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.

Biological: Raludotatug Deruxtecan · Drug: Paclitaxel · Drug: Rescue Medication

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

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.

Biological: Raludotatug Deruxtecan · Drug: Carboplatin · Drug: Rescue Medication

Cohort B-1 (R-DXd + Bevacizumab)

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

Biological: Raludotatug Deruxtecan · Biological: Bevacizumab · Drug: Rescue Medication

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

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.

Biological: Raludotatug Deruxtecan · Biological: Bevacizumab · Drug: Rescue Medication

Cohort C-1 (R-DXd + Pembrolizumab)

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.

Biological: Raludotatug Deruxtecan · Drug: Rescue Medication · Biological: Pembrolizumab

Cohort D (R-DXd +/- Bevacizumab)

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

Biological: Raludotatug Deruxtecan · Biological: Bevacizumab · Drug: Rescue Medication

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

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.

Biological: Raludotatug Deruxtecan · Drug: Carboplatin · Biological: Bevacizumab · Drug: Rescue Medication

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

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.

Biological: Raludotatug Deruxtecan · Drug: Paclitaxel · Biological: Bevacizumab · Drug: Rescue Medication

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

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.

Drug: Carboplatin · Drug: Paclitaxel · Biological: Bevacizumab · Drug: Gemcitabine · Drug: Pegylated liposomal doxorubicin

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

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.

Biological: Raludotatug Deruxtecan · Drug: Rescue Medication · Drug: MK-2010

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

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).

Biological: Raludotatug Deruxtecan · Drug: Carboplatin · Drug: Paclitaxel · Biological: Pembrolizumab

Cohort C-2 Arm 2 (Carboplatin + Paclitaxel)

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

Drug: Carboplatin · Drug: Paclitaxel

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

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.

Biological: Raludotatug Deruxtecan · Biological: Bevacizumab · Biological: Pembrolizumab

Raludotatug Deruxtecan BIOLOGICAL

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

Carboplatin DRUG

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

Paclitaxel DRUG

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

Bevacizumab BIOLOGICAL

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

Rescue Medication DRUG

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

Pembrolizumab BIOLOGICAL

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

Gemcitabine DRUG

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

Pegylated liposomal doxorubicin DRUG

IV injection administered on Day 1 of each 4-week cycle

MK-2010 DRUG

IV infusion on Day 1 of every 3-week cycle

Prepare your questions

What researchers are measuring

Outcome measures describe what is being studied. They are not proof that a treatment works.

Primary measures

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)

Time frame: 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)