A Study of Raludotatug Deruxtecan (R-DXd) in Subjects With Platinum-resistant, High-grade Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

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

Objective

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.

Eligibility

• 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 platinum-resistant disease. If a subject had only 1 line of platinum therapy, must have received at least 4 cycles of platinum, must have had a best response of not PD, and then progressed between >90 and ≤180 days after the date of the last dose of platinum If a subject had 2 or 3 lines of platinum therapy, must have received at least 2 cycles of platinum and have progressed on or within 180 days after the date of the last dose of platinum.
• Has had prior poly-ADP ribose polymerase (PARP) inhibitors for participants with documented breast cancer gene mutation (germline and/or somatic), unless the participant is not eligible for treatment with a PARP inhibitor.
• Has had prior treatment with mirvetuximab soravtansine for participants with documented high-folate receptor alpha expression, unless the participant is not eligible for treatment with mirvetuximab soravtansine due to precautions/intolerance, or if the treatment is not approved or available locally.
• Has at least 1 measurable lesion evaluated by computed tomography or magnetic resonance imaging according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) per investigator assessment.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Required baseline local laboratory data (within 7 days before start of study drug administration):
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
    • 3.0 × upper limit of normal (ULN) in subjects with no liver metastasis and
    • 5.0 × ULN in subjects with liver metastasis
  • Total bilirubin (TBL) ≤1.5 × ULN (<3 × ULN for subjects with Gilbert's syndrome or liver metastasis at baseline)
  • Absolute neutrophil count ≥1.5 × 109/L (growth factor support allowed up to 14 days before laboratory assessment for eligibility)
  • Platelet count ≥100 × 109/L (transfusion allowed up to 14 days before laboratory assessment for eligibility)
  • Hemoglobin ≥9.0 g/dL (transfusion and/or growth factor support allowed up to 14 days before laboratory assessment for eligibility)
  • Creatinine clearance ≥30 mL/min as calculated using the Cockcroft-Gault equation
  • Serum albumin ≥2.5 g/dL
  • Adequate blood clotting function: International normalized ratio and either activated partial thromboplastin time or partial thromboplastin time ≤1.5 × ULN, unless the subject is receiving anticoagulant therapy as long as activated partial thromboplastin time or partial thromboplastin time is within the therapeutic range of intended use of anticoagulants
• If the participant is a female of childbearing potential, she must have a negative serum pregnancy test at 72 hours before the first dose of study drug and must be willing to use highly effective birth control upon enrollment, during the Treatment Period, and for 7 months following the last dose of study drug. A female is considered of childbearing potential following menarche and until becoming postmenopausal (no menstrual period for a minimum of 12 months) unless permanently sterile (undergone a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) with surgery at least 1 month before the first dose or confirmed by follicle-stimulating hormone test.
• Female participants must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration.
• Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
• For Phase 3 (Part B) only: Participants must be eligible for one of the treatments included in the Investigator's choice of chemotherapy arm and must not have received it previously for OVC.

NCT ID

NCT06161025