Ac-225 rosopatamab tetraxetan (CONV01-α)

P1/2, N=76, Recruiting, Weill Medical College of Cornell University | Suspended --> Recruiting

P1, N=6, Active, not recruiting, Weill Medical College of Cornell University | Recruiting --> Active, not recruiting | N=18 --> 6

P1/2, N=76, Suspended, Weill Medical College of Cornell University | Recruiting --> Suspended | Trial primary completion date: Jun 2025 --> Jun 2026

P1/2, N=105, Suspended, Weill Medical College of Cornell University | Recruiting --> Suspended

P1/2, N=48, Suspended, Weill Medical College of Cornell University | Trial primary completion date: Dec 2024 --> Dec 2025

225Ac-PSMA-J591 effectively treats all metastatic categories. However, bone and visceral lesions may respond better than nodal lesions. Our findings need further validation but are informative for trial design and patient counselling.

P1; Active, not recruiting --> Completed | Trial completion date: Jul 2024 --> Sep 2023

P1; Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2025

NLR provides prognostic information in the setting of patients with mCRPC receiving treatment with PSMA-TRT.

P1, N=0, Withdrawn, Weill Medical College of Cornell University | N=24 --> 0 | Initiation date: Jun 2023 --> Dec 2023 | Not yet recruiting --> Withdrawn

P1/2; N=33 --> 48

Notably, radionuclide drug conjugates (RDC), specifically 177Lu/111In-J591 and 225Ac-J591, exhibited enhanced therapeutic efficacy in treating patients with CRPC. Furthermore, promising treatment approaches for CRPC included dual anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) blockade in rare tumors (DART)-Lorigerlimab, prostate stem cell antigen (PSCA)-directed chimeric antigen receptor (CAR)-T cell immunotherapy-BPX-601, and protein kinase inhibitor (AKTi)-CAPltello-280. We have summarized the latest CRPC treatment strategies presented at the 2023 ASCO-GU Cancers Symposium, along with recent advances in CRPC clinical trials.

P1/2; Recruiting --> Suspended

Median age 71 (IQR 66-77.5), PSA 57.3 ng/mL (21.3-294.9), 80 (44.4%) prior chemotherapy, 86 (47.7%) prior abiraterone or androgen receptor signaling inhibitor, 167 (92.8%) bone metastases, 141 (78.3%) nodal metastases, 113 (62.8%) CALGB high-risk group. 94 (52.2%) received 177Lu-J591, 51 (28.3%) 177Lu-PSMA-617, 28 (15.6%) 225Ac-J591, 7 (3.9%) 90Y-J591... For patients with mCRPC receiving PSMA TRT, NLR may have prognostic implications with higher NLR associating with lower likelihood of PSA response and shorter overall survival.

P1, N=24, Not yet recruiting, Weill Medical College of Cornell University | Initiation date: Dec 2022 --> Jun 2023

P1, N=24, Not yet recruiting, Weill Medical College of Cornell University

To investigate the role of PSMA expression and CRT membrane localization as a biomarker of response to PSMA-TRT, we isolated circulating tumor cells (CTCs) from patients with mCRPC, enrolled in a phase I dose escalation trial of 225Ac-J591 (NCT03276572)...Our preliminary results indicate higher expression of plasma membranous CRT in on-treatment CTCs in responders (PFS>12 months; n= 39 CTCs from 3 patients) than in non-responders (PFS<3 months; n= 20 CTCs from 2 patients). Full analysis of CRT and PSMA expression is currently being completed.

P1/2; N=33; Recruiting; Sponsor: Weill Medical College of Cornell University; Not yet recruiting --> Recruiting

P1/2, N=76, Not yet recruiting, Weill Medical College of Cornell University

P1/2; N=33; Not yet recruiting; Sponsor:Weill Medical College of Cornell University

P1; Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2021 --> Jan 2021

Forty-four patients (37.9%) received 177Lu-J951, 46 (39.7%) received 177Lu-PSMA-617, and 26 (22.4%) received 225Ac-J591. This is the largest analysis of CTC changes in patients who have received PSMA-TRT. In addition to PSA changes and other previously reported outcomes, even when low doses of radionuclide therapy as part of dose-escalation studies are included, the majority with detectable CTC counts have post-treatment CTC count decline. A significant portion of patients experience favorable CTC changes.

P1, N=18, Recruiting, Weill Medical College of Cornell University | Not yet recruiting --> Recruiting

P1, N=18, Not yet recruiting, Weill Medical College of Cornell University

P1/2, N=105, Recruiting, Weill Medical College of Cornell University | Not yet recruiting --> Recruiting

P1/2, N=105, Not yet recruiting, Weill Medical College of Cornell University

38 (57%) received 177Lu-PSMA-617, 16 (24%) 177Lu-J591, 7 (11%) 225Ac-J591, and 5 (8%) both 177Lu-PSMA-617 and 177Lu-J591. AR resistance mutations and amplifications appear to result in poorer outcome following PSMA-TRT both in terms of PSA decline and overall survival. Genetic sequencing may inform responses to PSMA-based therapies, and prospective genomic panel testing is ongoing.Supported by: Weill Cornell Medicine, Prostate Cancer Foundation, Department of Defense, NIH

Alpha-emitter 225Ac targeting PSMA via J591 Ab is tolerable with early evidence of clinical activity in a pre-treated population with favorable PRO’s. Enrollment to expansion cohort being completed. Research Funding: Weill Cornell Medicine, Other Foundation, Other Government Agency, U.S. National Institutes of Health

Following binding, immunoreactivity, and xenograft studies, we performed a first in human study of 225Ac-J591. Men with progressive mCRPC following at least 1 potent AR-targeted agent (e.g. abiraterone/enzalutamide) and taxane chemotherapy (or unfit/refuse chemo) without limit of # prior therapies (including radium-223 or prior PSMA therapy) provided adequate organ function were eligible. PSMA-targeted alpha-emitter 225Ac utilizing intact antibody J591 is tolerable with early evidence of clinical activity including long-term responders in a pre-treated population. Correlative studies are in progress and enrollment into a Simon 2-stage expansion cohort has been initiated. Clinicaltrials.gov NCT03276572