Ac-225 rosopatamab tetraxetan (CONV01-α) / Weill Cornell Medical College, Dominari Holdings - LARVOL DELTA

Dose-escalation + expansion trial of fractionated and multiple-dose PSMA-targeted alpha radionuclide 225Ac-J591 for mCRPC (ESMO 2025) - No abstract available

Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer

Re-treatment 225Ac-J591 for mCRPC (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Weill Medical College of Cornell University | Active, not recruiting ➔ Completed

Trial completion • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • CTCs

Fractionated and Multiple Dose 225Ac-J591 for Progressive mCRPC (clinicaltrials.gov) - P1/2 | N=60 | Active, not recruiting | Sponsor: Weill Medical College of Cornell University | Suspended ➔ Active, not recruiting | N=105 ➔ 60 | Trial completion date: Jun 2027 ➔ Jun 2026

Enrollment change • Enrollment closed • Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • CTCs

Phase I/II 225Ac-J591 Plus 177Lu-PSMA-I&T for Progressive Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1/2 | N=48 | Suspended | Sponsor: Weill Medical College of Cornell University | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • CTCs

CONVERGE-01: Dosimetry, Randomized Dose Optimization, Dose Escalation and Efficacy of Ac-225 Rosopatamab Tetraxetan in Participants with PSMA-Positive Castration-Resistant Prostate Cancer (SNMMI 2025) - "(No results as per Trials in Progress format)."

Clinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

CONVERGE-01: Dosimetry, Randomized Dose Optimization, Dose Escalation and Efficacy of Ac-225 Rosopatamab Tetraxetan in Participants with PSMA-Positive Castration-Resistant Prostate Cancer (SNMMI 2025) - "(No results as per Trials in Progress format)."

Clinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Single Time-Point SPECT/CT Dosimetry for 177Lu-PSMA targeted radionuclide therapy: Association with treatment response and PSMA-PET Biomarkers in mCRPC (SNMMI 2025) - P1/2 | " Patients with mCRPC treated with 177Lu-PSMA-617 monotherapy (PLUVICTO, Novartis) or 177Lu-PSMA-I&T plus 225Ac-J591, as part of a phase 1/2 dose-escalation trial (NCT04886986) conducted at our institution were retrospectively analyzed. Single time-point SPECT/CT dosimetry can provide useful dosimetric parameters to predict treatment response and provide feasible and more practical usage in routine clinical practice. Baseline PSMA-PET metrics, correlated with segmented tumors absorbed doses highlighting their potential value as predictive biomarkers for Lu177 PSMA accumulation. These findings underscore the importance of post-TRT SPECT/CT and highlight the need for further exploration to enable tailored, patient specific dosing of radionuclide therapy in mCRPC."

Biomarker • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

PSMA-targeted actinium-225 therapy in metastatic castration-resistant prostate cancer (mCRPC): Baseline and follow-up PSMA PET parameters associated with outcomes. (ASCO 2025) - P1, P1/2 | " Patients enrolled in phase I dose-escalation trials of 225Ac-J591, either as a single agent (NCT03276572, NCT04506567; n = 87) or in combination (with 177Lu-PSMA-I&T, NCT04886986, n = 18; or pembrolizumab and androgen receptor (AR) inhibitors, NCT04946370 n = 12), were included...Prior therapies included chemotherapy (62%), >1 AR pathway inhibitor (53%), immunotherapy (42%), 177Lu-PSMA (28%), and radium-223 (17%)... Higher baseline PSMA PET metrics, including SUVmean, SUVmax, and TTV are associated with PSA50 response and survival in patients receiving antibody-delivered alpha emitter 225Ac. Higher TTV, yielding more radionuclide delivery to tumor (most commonly bone) is associated with higher grade myelosuppression. However, the tumor antigen sink effect may decrease exposure to other PSMA+ organs leading to less xerostomia and nausea."

Metastases • Anemia • Castration-Resistant Prostate Cancer • Dental Disorders • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Xerostomia

PSMA-Targeted Actinium-225 Therapy in Metastatic Castration-Resistant Prostate Cancer: Comparative Outcomes Between Monotherapy vs. Combination Therapy (AUA 2025) - " Patients in Phase I dose-escalation trials of single agent 225Ac-J591 or 225Ac-J591 combinations (with 177Lu-PSMA-I&T or Pembrolizumab and Androgen Receptor Inhibitor) were included...Prior therapies included chemotherapy in 75 (63%), >1 AR pathway inhibitor in 61 (50%), immunotherapy in 49 (40%), 177Lu-PSMA in 34 (28%), and radium-223 in 20 (16%)... 225Ac-J591 in combination with other agents appears associated with better PFS and OS outcomes compared to single-agent therapy. Overall, improved efficacy does not appear to be at the cost of increased toxicity."

Combination therapy • Metastases • Monotherapy • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hematological Disorders • Neutropenia • Oncology • Pain • Prostate Cancer • Solid Tumor • Xerostomia

225Ac-J591 PSMA-Targeted Radionuclide Therapy in Metastatic Castration-Resistant Prostate Cancer Patients with Prior 177Lu-PSMA Therapy (AUA 2025) - P2 | "INTRODUCTION AND OBJECTIVE: Prostate-specific membrane antigen -targeted radioligand therapy (PSMA-TRT) with 177Lu-PSMA-617 is a validated approach; however, response rates vary, and disease progression is nearly inevitable. PSMA-targeted alpha radionuclide therapy using 225Ac-J591 has efficacy in patients with mCRPC despite prior 177Lu-PSMA. Common clinical prognostic factors are associated with poorer outcomes. A multicenter study is enrolling patients with and without prior 177Lu-PSMA to validate these findings [NCT06549465]."

Clinical • Metastases • Anemia • Castration-Resistant Prostate Cancer • Fatigue • Genito-urinary Cancer • Hematological Disorders • Neutropenia • Oncology • Pain • Prostate Cancer • Solid Tumor • Thrombocytopenia

Mature phase 1 follow up of alpha emitter 225Ac-J591 with 177Lu-PSMA-I&T in advanced prostate cancer. (ASCO-GU 2025) - P1/2 | "Here, we present mature follow up of a phase 1 dose-escalation trial of 225Ac-J591 plus 177Lu-PSMA-I&T (aka PNT2002)...Previous therapies: 11 (61%) with >1 ARPI, 12 (67%) chemo, 5 (28%) sip-T, 3 (17%) radium-223... The combination of PSMA-targeted alpha (via antibody) plus beta (via small molecule) was feasible. High grade AEs were rare and no new safety signals emerged with longer term follow up. Nearly all patients had PSA decline, and 5 had durable disease control off therapy."

Metastases • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

CONVERGE-01: Dosimetry, randomized dose optimization, dose escalation, and efficacy of ac-225 rosopatamab tetraxetan in participants with PSMA-positive castration-resistant prostate cancer. (ASCO-GU 2025) - P2 | "Exploratory endpoints include: rPFS, ORR, and DOR via RECIST v1.1 (PCWG3-modified where appropriate), genomic and imaging biomarker nomination. Enrollment began in August 2024."

Clinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

ASCO GU 2025: CONVERGE-01: Dosimetry, Randomized Dose Optimization, Dose Escalation, and Efficacy of Ac-225 Rosopatamab Tetraxetan in Participants with PSMA-Positive CRPC (UroToday) - "The phase II CONVERGE-01 trial in progress was presented by Dr. Morris, this is the first industry-sponsored study of CONV01-ɑ and will further advance the understanding of safety and efficacy in patients with progressive PSMA PET-positive CRPC....Notably, there are key differences between part 2 and part 3 in defining disease distribution for CRPC. Part 2 allows the inclusion of non-metastatic CRPC patients based on conventional imaging. Regardless of whether they are enrolled in part 2 or part 3, all patients must have PSMA PET–visualized disease. Moreover, in Part 3, patients are required to have been exposed to prior RLT....Enrollment in the CONVERGE-01 phase II study began in August 2024 and is ongoing in this multicenter study."

Trial status • Castration-Resistant Prostate Cancer

Convergent Therapeutics Announces Two Clinical Trial Updates on CONV01-α at the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium 2025 (PRNewswire) - P1/2 | N=48 | NCT04886986 | "The first presentation...reported clinical follow-up of a Phase I dose-escalation trial exploring the addition of CONV01-α to 177Lu-PSMA-I&T....Data showed that the median overall survival was 29.8 months, with 10 patients still alive at the time of submission. Five patients were free from PSA progression at one year including one patient progression-free at 34 months on no active therapy. A decline in prostate-specific antigen (PSA) levels was seen in 94% of patients, 64% of patients achieved a PSA50 and 28% achieved a PSA90 response....The second presentation, titled 'CONVERGE-01: Dosimetry, randomized dose optimization, dose escalation, and efficacy of Ac-225 rosopatamab tetraxetan in participants with PSMA-positive castration-resistant prostate cancer,' is a 'Trials in Progress' presentation of the three-part company sponsored Phase II trial..."

P1 data • Trial status • Castration-Resistant Prostate Cancer

Phase I/II Trial of Pembrolizumab and Androgen-receptor Pathway Inhibitor With or Without 225Ac-J591 for Progressive Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1/2 | N=76 | Recruiting | Sponsor: Weill Medical College of Cornell University | Suspended ➔ Recruiting

Enrollment open • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Re-treatment 225Ac-J591 for mCRPC (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Weill Medical College of Cornell University | Recruiting ➔ Active, not recruiting | N=18 ➔ 6

Enrollment change • Enrollment closed • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Mature follow up of phase I dose finding trial of pembrolizumab (pembro) with AR inhibitors (ARI) and priming tumour-targeted radiation with anti-PSMA alpha emitter 225Ac-J591 (ESMO 2024) - P1/2 | "Treatment: ARI of physician's choice (enza/apa/darolutamide), pembro (pembro 400mg every 6 weeks), and single infusion of 225Ac-J591 at two different dose levels (65 or 80 KBq/kg). The addition of 225Ac-J591 to pembro and ARI appears promising, with half of patients at 80 KBq/kg having durable response. The randomized phase II trial of pembro/ARI +/- 225Ac-J591 is ongoing (NCT04946370)."

IO biomarker • P1 data • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA2 • CHEK2 • PD-L1 • TMB

Convergent Therapeutics Announces First Patient Treated in Phase II Clinical Trial with Lead Therapeutic Candidate and Corporate Updates (PRNewswire) - "Convergent Therapeutics Inc...announced that the first patient has been dosed with CONV01-α in the Phase II CONVERGE-01 trial evaluating CONV01-α, Ac-225 rosopatamab tetraxetan, for the treatment of patients with prostate-specific membrane antigen (PSMA) PET-positive metastatic castration resistant prostate cancer (mCRPC)....'We look forward to evaluating the full potential of CONV01-α and advancing the Phase II trial in the months ahead'....Convergent announced a $40 million Series A extension by Novo Holdings, a holding and investment company wholly owned by the Novo Nordisk Foundation. This additional funding increases the total Series A raise to $130 million to support the development of Convergent's radiopharmaceutical pipeline, including CONV01-α."

Trial status • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

NorthStar Medical Radioisotopes and Convergent Therapeutics, Inc. Expand Strategic Collaboration Around CONV01-α (Businesswire) - "NorthStar Medical Radioisotopes, LLC...and Convergent Therapeutics, Inc...announced the signing of a strategic contract manufacturing services agreement....Under the terms of the expanded collaboration, NorthStar will: Provide Convergent with its environmentally preferred, high purity non-carrier-added (n.c.a) Ac-225 for use in CONV01-α, Utilize its new, state-of-the-art contract development and manufacturing facility to manufacture CONV01-α to serve patients in Convergent’s clinical trials, and Perform research and development activities to support continued development of CONV01-α and other Convergent assets."

Licensing / partnership • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Phase I/II Trial of Pembrolizumab and Androgen-receptor Pathway Inhibitor With or Without 225Ac-J591 for Progressive Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1/2 | N=76 | Suspended | Sponsor: Weill Medical College of Cornell University | Recruiting ➔ Suspended | Trial primary completion date: Jun 2025 ➔ Jun 2026

Metastases • Trial primary completion date • Trial suspension • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Fractionated and Multiple Dose 225Ac-J591 for Progressive mCRPC (clinicaltrials.gov) - P1/2 | N=105 | Suspended | Sponsor: Weill Medical College of Cornell University | Recruiting ➔ Suspended

Metastases • Trial suspension • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Phase I/II 225Ac-J591 Plus 177Lu-PSMA-I&T for Progressive Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1/2 | N=48 | Suspended | Sponsor: Weill Medical College of Cornell University | Trial primary completion date: Dec 2024 ➔ Dec 2025

Metastases • Trial primary completion date • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Phase I Dose-Escalation Trial of Multiple and Fractionated-Dose PSMA-Targeted Alpha Radionuclide (225Ac-J591) for Metastatic Castration-Resistant Prostate Cancer (AUA 2024) - P1/2 | "225Ac-J591 administered in a dose-dense fractionated regimen appears safe with preliminary efficacy; ongoing study to optimize the regimen for 177Lu-PSMA exposed and naïve is in progress. 225Ac-J591 at multiple doses q6 weeks does not appear optimal given timing of blood count nadir, but in a separate study, 225Ac-J591 in combo with 177Lu-PSMA-I&T administered at 8-week intervals appears promising."

Metastases • P1 data • Genito-urinary Cancer • Hematological Disorders • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • Thrombocytopenia

Descriptive analysis of patients with mCRPC and liver metastases receiving alpha and beta PSMA targeted radionuclide therapy (PSMA-TRT) (AACR 2024) - "Patients received alpha therapy (225Ac-J591), beta therapy (fractionated 177Lu-PSMA-617, single-dose and fractionated 177Lu-J591) or a combination of both (225Ac-591 and 177Lu-PSMA-I&T)... This dataset adds to the collective literature of two subgroups of patients with mCRPC receiving TRT: those with liver disease and those with mutations in DNA repair pathways. The results of this study suggest higher rates of response in patients receiving alpha therapy, either alone or in combination with beta therapy, and in patients with high radiotracer uptake on PSMA-PET, based on PSMA-imaging score of 3 or 4. Genomic alterations in DRR proteins did not have clear implications."

Clinical • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • BRCA2 • CHEK2 • MSH2 • TP53

Convergent Therapeutics Announces FDA Clearance of IND Application for CONV01-α, a Best-in-Class Radioantibody Targeting Prostate-Specific Membrane Antigen (PRNewswire) - "Convergent Therapeutics...announced that the U.S. Food and Drug Administration ('FDA') has cleared the investigational new drug ('IND') application for CONV01-α, its lead candidate for the treatment of patients with advanced prostate cancer....Convergent Therapeutics will conduct Phase 2 clinical trials in 2024 preparing for a registrational program in 2025."

IND • New P2 trial • Prostate Cancer