Clinical trial NCT06843447: A Clinical Study of Raludotatug Deruxtecan in People With Ovarian Cancer (MK-5909-003)
Official title: A Phase 1b/2 Open-label, Multicenter Study to Evaluate the Safety and Efficacy of Raludotatug Deruxtecan With or Without Other Anticancer Investigational Agents in Participants With High-grade Serous Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Have Relapsed After Prior Platinum-based Chemotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Ovarian Cancer Recurrent
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2025-02-25
Enrollment: 78
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 standard treatment and if people tolerate them together.


Eligibility criteria: 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 1 and Arm 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-sensitive disease).
* Participants in Cohort B-1: 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: 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

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

Primary outcomes:
measure: Number of Participants Who Experience a Dose-limiting Toxicity (DLT) Per Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0)
timeFrame: Up to 21 days
measure: Number of Participants with One or More Adverse Events (AEs)
timeFrame: Up to approximately 3 years
measure: Number of Participants who Discontinue Study Intervention Due to an AE
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
city: West Valley City
country: United States
facility: START Mountain Region ( Site 0008)
state: Utah
city: Haifa
country: Israel
facility: Rambam Health Care Campus ( Site 0202)
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center ( Site 0201)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center ( Site 0200)
city: L'Hospitalet de Llobregat
country: Spain
facility: Institut Català d'Oncologia - L'Hospitalet ( Site 0302)
state: Barcelona
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra ( Site 0301)
state: Madrid, Comunidad De
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 0300)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: