Study Name: DS6000-109

Recruiting

Ovarian Fallopian Tube or Primary Peritoneal

A Phase 2/3, Multicenter, Randomized Study of Raludotatug Deruxtecan (R-DXd), a CDH6-directed Antibody-drug Conjugate, in Subjects With Platinum-resistant, High-grade Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

NCT#NCT06161025

clinicaltrials.gov/show/NCTNCT06161025

This study will focus on R-DXd in participants with platinum-resistant, high-grade ovarian, primary peritoneal, or fallopian tube cancer. R-DXd is an antibody-drug conjugate that specifically binds to CDH6, which is overexpressed in tumor cells. The Phase 2 dose-optimization part of the study (Part A) intends to define the recommended dose based on safety and efficacy, while the Phase 3 (Part B) part of the study will compare R-DXd with Investigator’s choice of chemotherapy and further evaluate efficacy.

Female – 18 years and older

• Sign and date the informed consent form prior to the start of any study-specific qualification procedures
• Age ≥18 years or the minimum legal adult age (whichever is greater) at the time the informed consent form is signed
• Participants with histologically or cytologically documented high-grade serous ovarian cancer (OVC), high-grade endometrioid OVC, primary peritoneal cancer, or fallopian tube cancer
• Participants must have at least 1 lesion, not previously irradiated, amenable to biopsy, and must consent to provide a pretreatment biopsy and on-treatment biopsy tissue sample (on- treatment biopsy sample not required for the Phase 3 part of the study). Fresh pretreatment biopsy may be waived for subjects who consent to provide an archival tumor tissue sample from a lesion not previously irradiated, performed within 6 months of consent, and performed after treatment with their most recent cancer therapy regimen
• Has received at least 1 but no more than 3 prior systemic lines of anticancer therapy:
• Neoadjuvant +/-adjuvant considered 1 line of therapy
• Maintenance therapy (eg, bevacizumab, poly-ADP ribose polymerase [PARP] inhibitors) will be considered part of the preceding line of therapy
• Therapy changed due to toxicity in the absence of progression will be considered part of the same line
• Hormonal therapy will be counted as a separate line of therapy, unless it was given as maintenance
• At least 1 line of therapy containing bevacizumab, unless the subject is not eligible for treatment with bevacizumab due to precautions/intolerance. Note: Subjects must have progressed radiologically on or after their most recent line of systemic therapy. Biochemical progression will not be considered progression for this study

• Has clear cell, mucinous, or sarcomatous histology, mixed tumors containing any histology, or low-grade/borderline OVC
• Clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis, defined as untreated or symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Subjects with untreated and asymptomatic brain metastases or subjects with treated brain metastases who are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy, at the investigator's discretion. Note: If there is a history or suspicion of central nervous system metastasis, a CT scan of the head or MRI of the brain must be performed at baseline
• Any of the following within the past 6 months prior to randomization: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event
• Uncontrolled or significant cardiovascular disease
• Inadequate washout period before Cycle 1 Day 1, defined as follows:
• Major surgery <28 days
• Radiation therapy <28 days (if palliative stereotactic radiation therapy without abdominal radiation, ≤14 days)
• Systemic anticancer therapy (including antibody-drug therapy, retinoid therapy, and hormonal therapy) <28 days or 5 half-lives, whichever is shorter, before starting study drug
• Chloroquine/hydroxychloroquine <14 days
• Exposure to another investigational drug within 28 days prior to start of study treatment or current participation in other therapeutic investigational procedures