Phase I trial of ¹⁷⁷Lutetium-labeled J591, a monoclonal antibody to prostate-specific membrane antigen, in patients with androgen-independent prostate cancer

Purpose: To determine the maximum tolerated dose (MTD), toxicity, human anti-J591 response, pharmacokinetics (PK), organ dosimetry, targeting, and biologic activity of ¹⁷⁷Lutetium-labeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (¹⁷⁷Lu-J591) in patients with androgen-independent prostate cancer (PC). Patients and Methods: Thirty-five patients with progressing androgen-independent PC received ¹⁷⁷Lu-J591. All patients underwent ¹⁷⁷Lu-J591 imaging, PK, and biodistribution determinations. Patients were eligible for up to three retreatments. Results: Thirty-five patients received ¹⁷⁷Lu-J591, of whom 16 received up to three doses. Myelosuppression was dose limiting at 75 mCi/m², and the 70-mCi/m² dose level was determined to be the single-dose MTD. Repeat dosing at 45 to 60 mCi/m² was associated with dose-limiting myelosuppression; however, up to three doses of 30 mCi/m ² could be safely administered. Nonhematologic toxicity was not dose limiting. Targeting of all known sites of bone and soft tissue metastases was seen in all 30 patients with positive bone, computed tomography, or magnetic resonance images. No patient developed a human anti-J591 antibody response to deimmunized J591 regardless of number of doses. Biologic activity was seen with four patients experiencing ≥ 50% declines in prostate-specific antigen (PSA) levels lasting from 3+ to 8 months. An additional 16 patients (46%) experienced PSA stabilization for a median of 60 days (range, 1 to 21 + months). Conclusion: The MTD of ¹⁷⁷Lu-J591 is 70 mCi/m². Multiple doses of 30 mCi/m² are well tolerated. Acceptable toxicity, excellent targeting of known sites of PC metastases, and biologic activity in patients with androgen-independent PC warrant further investigation.