Phase II trial of 177Lutetium radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (177Lu- J591) in patients (pts) with metastatic castrate-resistant prostate cancer (metCRPC)

Tagawa, Scott T.; Milowsky, Mathew I.; Morris, M. J.; Vallabhajosula, Shankar; Goldsmith, Stanley J.; Matulich, Dan; Kaplan, Jason; Berger, Frédérique; Scher, Howard I.; Bander, Neil H.; Nanus, David M.

doi:10.1200/jco.2008.26.15_suppl.5140

Cited by 26 publications

(25 citation statements)

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“…(53, 54) In preliminary review of our overall anti-PSMA-based RIT experience through 2009 (109 patients), excluding re-treated patients, 98% and 87% had full recovery of neutrophils and platelets respectively. (55) Of the remaining, all but 4 recovered to Gr 1 neutropenia and/or thrombocytopenia. The most common reason for lack of complete hematologic recovery was CRPC progression (PSA and or scan progression with confirmatory bone marrow biopsy revealing significant prostate cancer metastases).…”

Section: Discussionmentioning

confidence: 94%

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

Tagawa

Milowsky

Morris

et al. 2013

Clinical Cancer Research

378

310

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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.

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Section: Discussionmentioning

confidence: 94%

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

Tagawa

Milowsky

Morris

et al. 2013

Clinical Cancer Research

378

310

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“…A second phase 1 trial utilizing 177 Lu-J591 in patients with CRPC demonstrated that fractioned dosing allowed for higher cumulative doses with less toxicity. 52 A third phase 1 clinical trial in patients with CRPC receiving docetaxel, prednisone, and escalating doses of 177 Lu-J591 is currently accruing patients.…”

Section: Resultsmentioning

confidence: 99%

The prostate-specific membrane antigen: Lessons and current clinical implications from 20 years of research

Ristau

O’Keefe

Bacich

2014

Urologic Oncology: Seminars and Original Investigations

144

123

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Objective Despite a multitude of detection and treatment advances in the past two decades, prostate cancer remains the second leading cause of cancer death among men in the United States. Technological evolution and expanding knowledge of tumor biomarkers have invigorated exploration in prostate cancer therapeutics. Prostate-specific membrane antigen (PSMA) was one of the first prostate cancer biomarkers successfully cloned. Since that time, it has been characterized as the prototypical cell-surface marker for prostate cancer and has been the subject of intense clinical inquiry. We review the relevant research in PSMA on the 20th anniversary of its cloning. Methods and materials A PubMed® search using the keywords “prostate-specific membrane antigen” or “glutamate carboxypeptidase II” provided 1019 results. An additional 3 abstracts were included from scientific meetings. Articles were vetted by title and abstract with emphasis placed on those with clinically relevant findings. Results Sixty articles were selected for inclusion. PSMA was discovered and cloned in 1993. Its structure and function were further delineated in the ensuing decade. Consensus sites of expression in normal physiology are prostate, kidney, nervous system, and small intestine. PSMA has been implicated in the neovasculature of several tumors including urothelial and renal cell carcinomas. In prostate cancer, expression of PSMA is directly related to Gleason grade. PSMA has been tested both in imaging and therapeutics in a number of prostate cancer clinical trials. Several recent approaches to target PSMA include use of small molecule inhibitors, PSMA-based immunotherapy, RNA aptamer conjugates, and PSMA-targeted prodrug therapy. Future study of PSMA in prostate cancer might focus on its intracellular functions and possible role in tumor neurogenesis. Conclusions Twenty years from its discovery, PSMA represents a viable biomarker and treatment target in prostate cancer. Research to delineate its precise role in prostate carcinogenesis and within the therapeutic armamentarium for patients with prostate cancer remains encouraging.

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“…Based upon the phase I results described above,37 a phase II trial was initiated at two centers and has now completed enrollment 38. Subjects with progressive metastatic castrate resistant prostate cancer received one dose of 177 Lu -J591 in two-cohorts.…”

Section: Phase II Trial Of 177lu -J591 For Metastatic Crpcmentioning

confidence: 99%

Anti–prostate‐Specific membrane antigen‐based radioimmunotherapy for prostate cancer

Tagawa

Beltran

Vallabhajosula

et al. 2010

Cancer

122

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Despite recent advances, advanced prostate cancer is suboptimally responsive to current chemotherapeutic agents. Radiolabeled monoclonal antibody therapy that targets prostate-specific membrane antigen (PSMA) shows promise and is an area of active investigation. J591 is a deimmunized IgG monoclonal antibody developed to target the extracellular domain of PSMA. Preclinical and early phase clinical studies using radiolabeled J591 have demonstrated efficacy in targeting tumor cells and decreasing levels of prostate-specific antigen. Radiolabeled J591 is well-tolerated, nonimmunogenic, and can be administered in multiple doses. The dose-limiting toxicity is reversible myelosuppression with little nonhematologic toxicity. Future studies will include approaches to optimize patient selection and incorporate novel strategies to improve the success of anti-PSMA radioimmunotherapy. Cancer 2010;116(4 suppl):1075-83.

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Phase II trial of 177Lutetium radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (177Lu- J591) in patients (pts) with metastatic castrate-resistant prostate cancer (metCRPC)

Cited by 26 publications

References 0 publications

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

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

The prostate-specific membrane antigen: Lessons and current clinical implications from 20 years of research

Anti–prostate‐Specific membrane antigen‐based radioimmunotherapy for prostate cancer

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