REJOICE-PanTumor01: A phase 2 signal-seeking study of raludotatug deruxtecan (R-DXd) in patients with advanced or metastatic gynecologic or genitourinary tumors.
Background: Cadherin-6 (CDH6), a transmembrane protein involved in cell–cell adhesion and epithelial–mesenchymal transition, is overexpressed in many cancer types. R-DXd is an anti-CDH6 antibody–drug conjugate composed of a humanized CDH6 antibody covalently linked to a potent topoisomerase I inhibitor payload (DXd) via a plasma-stable linker. In an ongoing Phase 1 study (NCT04707248), a subgroup of patients with heavily pretreated ovarian cancer (OC) who received R-DXd 4.8–6.4 mg/kg, had an objective response rate (ORR) of 48.6% (95% confidence interval [CI], 31.9–65.6); median duration of response (DOR) was 11.2 months (95% CI, 3.1–not estimable), and progression-free survival (PFS) was 8.1 months (95% CI, 5.3–not estimable), irrespective of CDH6 expression level (data cut-off: July 14, 2023). The safety profile of R‑DXd was manageable. In total, 11.1% of patients discontinued R-DXd due to treatment-emergent adverse events. These promising data warranted further investigation of R-DXd in REJOICE-Ovarian01 (NCT06161025), a Phase 2/3 study in patients with platinum-resistant high-grade serous OC (HGSOC), and in the REJOICE-PanTumor01 Phase 2 study, which is described here. Methods: REJOICE-PanTumor01 (NCT06660654) is a global, open-label Phase 2 study in patients with locally advanced or metastatic gynecologic (endometrial cancer [EC], cervical cancer, or non-HGSOC) or genitourinary (urothelial cancer [UC] or clear cell renal cell carcinoma [ccRCC]) tumors. Cohorts are tumor type–specific; patients in all cohorts must have relapsed or progressive disease after receiving ≥1 prior line (and ≤3 prior lines in the EC, UC, and ccRCC cohorts only) of standard treatment. Adult patients with ECOG performance status 0–1 are eligible; there is no selection for tumor CDH6 expression. Approximately 40 patients will be enrolled into each cohort to receive R-DXd 5.6 mg/kg IV every 3 weeks until disease progression per RECIST 1.1, unacceptable toxicity, death, or other reason per protocol. In each cohort, a nonbinding futility interim analysis will be conducted after 20 patients complete a minimum of 12 weeks of follow-up, the results of which may determine whether the remaining (~20) patients will be treated. Primary endpoints are ORR for the gynecological and UC cohorts, disease control rate (DCR) for the ccRCC cohort (both investigator-assessed), and safety and tolerability for all cohorts. Secondary endpoints are ORR (ccRCC cohort only), DCR (except ccRCC cohort), PFS, DOR, time to response (all investigator-assessed per RECIST 1.1), pharmacokinetics, and immunogenicity. No formal hypothesis testing will be performed; ORR and DCR will be analyzed using a Clopper–Pearson method to determine 95% CI. PFS and DOR will be analyzed using the Kaplan–Meier method (2-sided 95% CI). Study enrollment began in January 2025.
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Author Details
Laurence Albiges
Gustave Roussy, Paris Saclay University, Paris, France
Abstract Details
Meeting
2025 ASCO Annual Meeting
Session Type
Poster Session
Session Title
Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Track
Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
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