Recruiting
Phase 1
Phase 2

R-DXd with Chemotherapy

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT06843447

Conditions

Ovarian Cancer Recurrent

Eligibility Criteria

Sex: Female

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Raludotatug Deruxtecan

Carboplatin

Paclitaxel

Bevacizumab

Rescue Medication

Study Details

Brief 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.

Conditions

Ovarian Cancer Recurrent

Study ID

NCT06843447

Start date

Apr 15, 2025

Status verified date

Aug, 2026

Completion date

Feb 7, 2031

Anticipated

Primary completion date

Mar 27, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Female

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

605 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

experimental: 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.

experimental: 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.

experimental: Cohort B-1 (R-DXd + Bevacizumab)

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

experimental: 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.

experimental: 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.

experimental: 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.

experimental: 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.

experimental: 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.

active comparator: 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.

experimental: 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.

experimental: 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).

experimental: 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.

experimental: 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.

Interventions

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

Primary outcome measure

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

Central Contacts and Locations

Central contacts

Toll Free Number

1-888-577-8839Trialsites@msd.com

Locations

Yale-New Haven Hospital-Smilow Cancer Hospital at Yale-New Haven ( Site 0019)

Recruiting

New Haven, Connecticut, United States, 06510

Contacts

Study Coordinator

203-785-2404

The University of Louisville, James Graham Brown Cancer Center ( Site 0009)

Recruiting

Louisville, Kentucky, United States, 40202

Contacts

Study Coordinator

502-562-3429

TRIALS 365 ( Site 0020)

Recruiting

Shreveport, Louisiana, United States, 71103

Contacts

Study Coordinator

318-408-1198

Dana-Farber Cancer Institute ( Site 0015)

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Study Coordinator

877-338-7425

Memorial Sloan Kettering Cancer Center ( Site 0003)

Recruiting

New York, New York, United States, 10065

Contacts

Study Coordinator

212-639-2000

OU Health University of Oklahoma Medical Center ( Site 7000)

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contacts

Study Coordinator

405-271-1112

Texas Oncology - DFW ( Site 8000)

Recruiting

Fort Worth, Texas, United States, 76104

Contacts

Study Coordinator

615-329-7430

START Mountain Region ( Site 0008)

Recruiting

West Valley City, Utah, United States, 84119

Contacts

Study Coordinator

801-907-4750

University of Virginia Health System ( Site 0011)

Recruiting

Charlottesville, Virginia, United States, 22908

Contacts

Study Coordinator

434-924-9333

Centre Hospitalier de l'Université de Montréal ( Site 0102)

Recruiting

Montreal, Quebec, Canada, H2X 0A9

Contacts

Study Coordinator

514-890-8000

McGill University Health Centre ( Site 0100)

Recruiting

Montreal, Quebec, Canada, H4A 3J1

Contacts

Study Coordinator

514-934-1934x31975

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Sep 2, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-09-02.