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

225Ac-J591 PSMA-Targeted Radionuclide Therapy in Metastatic Castration-Resistant Prostate Cancer Patients with Prior 177Lu-PSMA Therapy (AUA 2025) - No abstract available

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

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

SUO 2023: Advances in Prostate Cancer (Cancer Therapy Advisor) - P1 | N=32 | NCT03276572 | "The fact that responses were higher in visceral lesions and bone than in lymph nodes is 'a little bit of a surprise,' said Oliver Sartor, MD...who was not involved in this study...'We know virtually nothing about alpha resistance or even if it exists,' Dr Sartor said. 'But I kind of believe if you get the right alpha to the right spot, you're probably going to kill a cell. Alphas are really big particles, and they're really quite destructive.'"

P1 data

SUO 2023: Advances in Prostate Cancer (Cancer Therapy Advisor) - P1 | N=32 | NCT03276572 | "In another presentation at SUO 2023, researchers reported results from a phase 1 trial of 225Ac-J591 (ClinicalTrials.gov Identifier: NCT03276572)....The rate of response was 71% in visceral lesions, 52% in bone, and 39% in lymph nodes. The complete response rates were 9%, 7%, and 4%, respectively....The results showed similar genomic risk distribution between the registries. The proportion of patients classified as high genomic risk was 31.4% in the GRID registry and 35.7% in the MUSIC registry. The proportion classified as intermediate risk was 18.5% in GRID and 16.2% in MUSIC. The proportion classified as low genomic risk was 50.2% and 47.9%, respectively."

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

ASSESSMENT OF PSMA PET IMAGING RESPONSE IN METASTATIC CASTRATION-RESISTANT PROSTATE CANCER AFTER 225AC-J591 THERAPY: POST-HOC PATIENT-LEVEL ANALYSIS OF A PROSPECTIVE CLINICAL TRIAL (SUO 2023) - "Our study demonstrates that 225Ac-PSMA-J591 shows promising efficacy in treating all metastatic categories, with particularly favorable responses observed in traditionally more difficult to treat bone and visceral lesions relative to nodal lesions. The analysis of 4 patients with liver metastases revealed encouraging outcomes, showing a significant decrease in PSA post-treatment, indicative of a positive therapeutic response. Although further validation is necessary, our findings hold significant implications for future trial design and patient counseling, underscoring the therapeutic potential of 225Ac-PSMA-J591 in managing advanced prostate cancer."

Clinical • Metastases • Retrospective data • Genito-urinary Cancer • Hepatology • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • CTCs

Metastatic Castration-Resistant Prostate Cancer: Efficacy of Anti-PSMA Antibody With Alpha Emitter (THE ASCO POST) - "In a phase I study reported in the Journal of Clinical Oncology, Scott T. Tagawa, MD, MS, FASCO, FACP, and colleagues determined the recommended phase II dose and described preliminary activity of actinium-225–J591-an anti–prostate-specific membrane antigen (PSMA) monoclonal antibody (J591) radiolabeled with the alpha emitter actinium-225-in patients with metastatic castration-resistant prostate cancer."

Online posting

PSMA PET Imaging Response Following a Single Dose 225AC J591 Therapy in Metastatic Castration Resistant Prostate Cancer: A Lesion and Patient Based Analysis (RSNA 2023) - P1 | "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."

Clinical • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1

PSMA-targeted agent 225Ac-J591 shows promising safety and efficacy in mCRPC (Urology Times) - P1 | N=32 | NCT03276572 | "The alpha prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy 225Ac-J591 demonstrated promising clinical efficacy and safety in patients with metastatic castration-resistant prostate cancer (mCRPC), according to data from a first-in-human phase 1 dose escalation trial (NCT03276572) of the agent....The median progression-free survival was 5.6 months (95% CI, 3.7-7.9) and the median overall survival was 10.7 months (95% CI, 6.5-17.2) among all patients. Only Cancer and Leukemia Group B prognostic grouping was found to be associated with survival (HR, 3.94; P = .04) upon multivariable analysis."

P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

New Radiopharmaceutical Shows Antitumor Activity in Patients with Advanced Prostate Cancer (Urotoday) - "'Despite considerable advances to improve prostate cancer survival, there is no cure yet for metastatic prostate cancer,' said lead author and principal investigator of the trial Dr. Scott Tagawa....'These strong results are due to the multidisciplinary collaboration between medical oncologists and our nuclear medicine group,' said Dr. Tagawa..."

Media quote

7R01CA207645-03: Phase I Trial of 225Ac-J591 in Patients With mCRPC (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Weill Medical College of Cornell University | Active, not recruiting ➔ Completed | Trial completion date: Jul 2024 ➔ Sep 2023

Metastases • Trial completion • Trial completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CTCs

Re-treatment 225Ac-J591 for mCRPC (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Weill Medical College of Cornell University | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Dec 2023 ➔ Dec 2025

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