Introduction:

Targeted radionuclide therapy (TRT) can localize treatment to specific tumor cells to reduce or eliminate damage to normal tissue. Prostate-specific membrane antigen (PSMA) is an ideal therapeutic target as it is highly expressed by malignant prostate cancer (PC) cells. 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. ¹⁷⁷Lu-rosopatamab is currently being investigated in this 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).

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, 14d 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 14d apart.

Eligible patients must have PSMA-expressing mCRPC and have experienced disease progression on a minimum 12w prior therapy on their 1^st 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 ORR, 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 sponsored by Telix Pharmaceuticals and is currently enrolling in Part 1. ClinicalTrials.gov ID: NCT06520345

Results:

Conclusion:

Funding: Telix Pharmaceuticals