DS6000-109 - 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 (Dose Optimization and Phase 3 Study of R-DXd versus Investigator’s Choice of Chemotherapy in Platinum resistant Ovarian Cancer)

Research summary

This is a global, multicenter, randomized, open-label, Phase 2/3 study in subjects with platinum-resistant, high-grade ovarian, primary peritoneal, or fallopian tube cancer who have received at least 1 and no more than 3 prior systemic lines of anticancer therapy. In this operationally seamless design, data from Phase 2 will not be utilized for the primary analysis in Phase 3 to strictly control the type I error in Phase 3. Phase 2 Study Design The Phase 2 part of this study is designed to randomize approximately 105 subjects to receive R-DXd at doses of 4.8, 5.6, or 6.4 mg/kg in a 1:1:1 ratio (ie, approximately 35 subjects in each group). Randomization will be stratified by the number of prior lines of therapy (1 vs. 2/3) and cadherin-6 (CDH6) protein expression in tumor tissue (CDH6 high vs. CDH6 low). The primary objective of the Phase 2 part is to identify the optimal dose of R-DXd for further clinical development. Enrollment may continue during the analysis of dose selection after the enrollment of 105 subjects in the 3 dose level cohorts, leading to enrollment of approximately 45 additional subjects (ie, 15 subjects in each group). The Phase 2 part may be further expanded to enroll at least 50 additional subjects at the selected dose to characterize efficacy and safety at the selected dose if justified by the outcome of the dose-selection analysis. Thus, the total sample size in Phase 2 may reach approximately 200 subjects. Phase 3 Study Design The Phase 3 part of this study is designed to randomize approximately 450 subjects to receive either R-DXd or investigator’s choice of chemotherapy in a 1:1 ratio (ie, approximately 225 subjects in each group). Randomization will be stratified by the number of prior lines of therapy (1 vs. 2/ 3), investigator’s choice of chemotherapy (paclitaxel vs. others), and CDH6 protein expression in tumor tissue (CDH6 high vs. CDH6 low).

Principal Investigator

Dr Rene Roux

Contact us

Email: latephaseoncology@ouh.nhs.uk

IRAS number

1009458