3351 - ProstACT Global: A Phase 3 Study of Lutetium (Lu177) Rosopatamab Tetraxetan<sup> </sup>plus Standard of Care vs. Standard of Care Alone in Patients with Metastatic Castration-Resistant Prostate Cancer
Presenter(s)
S. T. Tagawa1, N. Agarwal2, D. Cade3, A. O. Sartor4, and D. L. Boothe5; 1Division of Hematology & Medical Oncology, Weill Cornell Medical College, New York, NY, 2Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 3Telix Pharmaceuticals, Melbourne, Australia, 4Mayo Clinic, Rochester, MN, 5Intermountain Health, Salt Lake City, UT
Purpose/Objective(s): Targeted radionuclide therapy can localize treatment to specific tumor cells to reduce or eliminate damage to normal tissue for patients with prostate cancer (PC). Prostate-specific membrane antigen (PSMA) is an ideal therapeutic target as it is highly expressed by malignant PC cells. Compared to peptide-based, monoclonal antibody-based approaches have high binding specificity, rapid internalization, and long retention. Prior studies have demonstrated a favorable safety profile & efficacy of the radio-antibody drug conjugate (rADC) lutetium (Lu 177) rosopatamab tetraxetan (177Lu-rosopatamab) using a fractionated 2 dose regimen. Thus, 177Lu-rosopatamab is currently being investigated in a Phase 3 study for treatment of patients with PSMA+ metastatic castration resistant PC (mCRPC) who have received prior treatment with one androgen receptor pathway inhibitor (ARPI).
Materials/Methods: This multinational, multicenter, prospective, randomized, open label phase 3 study has 2 parts: a dosimetry and safety lead-in (Part 1; n=30) & a randomized treatment expansion (Part 2; n=490). In Part 1, patients are divided into 3 groups (n=10 each) to receive 2 single intravenous injections of 76 mCi each, 14 days apart, of 177Lu-rosopatamab with standard of care (SoC) combinations with abiraterone, enzalutamide, or docetaxel to characterize biodistribution & safety profiles of 177Lu-rosopatamab + SoC combinations. SoC received is determined prior to treatment with 177Lu-rosopatamab. In Part 2, patients will be enrolled 2:1 to receive SoC (determined pre-randomization) with or without 2 single injections of 76 mCi each of 177Lu-rosopatamab, given 14 days apart.
Eligible patients must have PSMA-expressing mCRPC and have experienced disease progression on a minimum 12w prior therapy on their 1st ARPI (abiraterone, apalutamide, darolutamide, or enzalutamide) in metastatic castration-sensitive PC, non-metastatic CRPC, or mCRPC settings. Patients may have received docetaxel in mCSPC setting provided last dose was =6m prior to screening. Patients must have PSMA+ disease on 68Ga-PSMA-11 PET/CT imaging. The primary endpoint is rPFS. Key secondary endpoint is OS. Additional secondary endpoints include 5-year OS, tumor objective response rate, time to symptomatic skeletal event, & health-related quality of life. An alpha control & 95% confidence intervals will be used; patients will be randomly assigned to receive 177Lu-rosopatamab + SoC or SoC alone. This study is currently enrolling and is sponsored by Telix Pharmaceuticals.Results: TBD
Conclusion: TBD