Phase II Study of Lutetium-177–Labeled Anti-Prostate-Specific Membrane Antigen Monoclonal Antibody J591 for Metastatic Castration-Resistant Prostate Cancer

Abstract

Purpose To assess the efficacy of a single infusion of radiolabeled anti-prostate specific membrane antigen monoclonal antibody J591 (177Lu-J591) by PSA decline, measurable disease response, and survival. Experimental Design In this dual-center phase II study, 2 cohorts with progressive metastatic castration-resistant prostate cancer received one dose of 177Lu-J591 (15 patients at 65 mCi/m2, 17 at 70 mCi/m2) with radionuclide imaging. Expansion cohort (n=15) received 70 mCi/m2 to verify response rate and examine biomarkers. Results 47 patients who progressed after hormonal therapies (55.3% also received prior chemotherapy) received 177Lu-J591. 10.6% experienced ≥ 50% decline in PSA, 36.2% experienced ≥ 30% decline, and 59.6% experienced any PSA decline following their single treatment. One of 12 with measurable disease experienced a partial radiographic response (8 with stable disease). Sites of prostate cancer metastases were targeted in 44 of 47 (93.6%) as determined by planar imaging. All experienced reversible hematologic toxicity with grade 4 thrombocytopenia occurring in 46.8% (29.8% received platelet transfusions) without significant hemorrhage. 25.5% experienced grade 4 neutropenia with 1 episode of febrile neutropenia. The phase I maximum tolerated dose (70 mCi/m2) resulted in more 30% PSA declines (46.9% vs 13.3%, p=0.048) and longer survival (21.8 vs 11.9 months, p=0.03), but also more grade 4 hematologic toxicity and platelet transfusions. No serious non-hematologic toxicity occurred. Those with poor PSMA imaging were less likely to respond. Conclusion A single dose of 177Lu-J591 was well-tolerated with reversible myelosuppression. Accurate tumor targeting and PSA responses were seen with evidence of dose-response. Imaging biomarkers appear promising.

German Multicenter Study Investigating177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

“…of 177 Lu-labeled J591 monoclonal antibody was associated with grade 4 thrombocytopenia in 47% of patients (23). In the present study, only 4% of the patients experienced a grade $ 3 thrombocytopenia.…”

Targeted Chemoradiation in Metastatic Colorectal Cancer: A Phase I Trial of 131I-huA33 with Concurrent Capecitabine

“…The optimization of antibody kinetics (e.g., multistep targeting) and isotopes (e.g., 177 Lu) has also emerged as an important factor in improving response rates (36,38). In view of the impressive results recently reported for 177 Lu and 90 Y peptide receptor therapy in the treatment of neuroendocrine tumors (39,40), it is clear that targeted radiation to tumors has significant potential for therapeutic efficacy, and our study provides further evidence of the potential for this approach.…”

Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

“…Those men with progressive disease who do not respond to 177 Lu PSMA therapy range from 10% to 32%. One of the larger studies, with 56 men enrolled, had 80% of all men enrolled had a PSA response to therapy3 All currently published studies with 177 Lu PSMA therapy in prostate cancer are retrospective, mostly single arm, and involve a variety of treatment regimens, both in terms of dose given (ranging from 3.5 to 8.0 Gbq/injection of Lu PSMA) and the number of doses administered (ranges from a single injection up to 4–6 injections 6 weeks apart) 2, 3, 4, 5, 6, 8, 9, 27, 39. This makes interpretation of the efficacy of the treatment difficult at this stage.…”