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

Phase I/II Trial of Pembrolizumab and Androgen-receptor Inhibitor With or Without 225Ac-J591 for Progressive Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1/2 | N=37 | Active, not recruiting | Sponsor: Weill Medical College of Cornell University | Recruiting ➔ Active, not recruiting | N=76 ➔ 37

Enrollment change • Enrollment closed • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • 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

Patient-reported outcomes (PRO) from a dose-escalation and expansion trial of fractionated and multiple-cycle PSMA-targeted alpha radionuclide 225Ac-J591. (ASCO-GU 2026) - P1/2 | "Clinical Trial Registry Number: NCT04506567. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

Clinical • Patient reported outcomes • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A phase I/II dose-escalation study of fractionated 225Ac-J591 for progressive metastatic castration-resistant prostate cancer (mCRPC) in patients with prior treatment with 177Lu-PSMA. (ASCO-GU 2023) - P1/2 | "With approval of 177Lu vipivotide tetraxetan, we amended an ongoing phase I dose-escalation study to include a post-177-Lu-PSMA cohort. Enrollment to the post-177Lu-PSMA cohort began in August 2022. Clinical trial information: NCT04506567."

Clinical • Metastases • P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Phase I dose-escalation study of fractionated dose 225Ac J591 for metastatic castration resistant prostate cancer (AACR 2023) - "Background: PSMA-based targeted radionuclide therapy is now a standard of care for mCRPC since approval of 177Lu-PSMA-617. A single fractionated cycle of 225Ac-J591 was delivered with few high grade AEs and with evidence of preliminary efficacy by PSA and CTC changes across all dose levels."

Metastases • P1 data • 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

Phase I dose-escalation results of prostate-specific membrane antigen-targeted radionuclide therapy (PSMA-TRT) with alpha-radiolabeled antibody 225Ac-J591 and beta-radioligand 177Lu-PSMA I&T. (ASCO 2023) - P1/2 | "Clinical Trial Registration Number: NCT04886986."

P1 data

Convergent Therapeutics and NorthStar Medical Radioisotopes Announce Expanded Partnership to Support Convergent's Late-Stage Alpha-Emitting Radioantibody Program (PharmiWeb) - "Co-locating Convergent’s manufacturing at NorthStar establishes an integrated and reliable supply chain for CONV01-α drug product production with Ac-225, relieving supply constraints for alpha-based radiotherapies and supporting Convergent’s ongoing clinical trials through to commercial production."

Commercial • Castration-Resistant Prostate Cancer

Long-term adverse events (AEs) in PSMA targeted radionuclide therapy (TRT) for castration-resistant prostate cancer (CRPC) (ESMO 2025) - P1, P1/2, P2, P3 | "59 patients received 177Lu-J591 (51%), 19 (16%) 177Lu-PSMA-617, 25 (22%) 225Ac-J591, 8 (7%) 225Ac-J591 + 177Lu-PSMA-I&T, 4 (3%) 177Lu-PSMA-I&T, and 1 (1%) 90Y-J591. Table: 2404P Category of adverse events (AEs) by grade and number of cases attributed to a cause other than PSMA-targeted radionucleotide therapy AE Type AE (%) Grade 1 (n) Grade 2 (n) Grade 3 (n) Grade 4 (n) Alternate cause in AEs Grades 3-4 (%) Kidney Injury 32 (28) 6 19 3 4 5/7 (71) Elevated trasnaminases 40 (34) 25 12 0 3 2/3 (66) Elevated bilirubin 16 (14) 4 5 3 4 6/7 (86) Neutropenia 11 (9) 5 2 1 3 4/4 (100) Thrombocytopenia 57 (49) 24 14 10 9 18/19 (95) Anemia 79 (68) 34 24 17 4 19/21 (90) Conclusions To our knowledge, this is the largest updated study of long-term AEs on prospective trials of PSMA-TRT. Secondary cancers and renal, liver, and marrow toxicities exist, but are not commonly observed."

Adverse events • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Dose-escalation + expansion trial of fractionated and multiple-dose PSMA-targeted alpha radionuclide 225Ac-J591 for mCRPC (ESMO 2025) - P1/2, P2 | "Multiple doses q6 weeks not recommended given timing of blood count nadir. Multicenter study underway to validate FD results with or without prior 177 Lu-PSMA [NCT06549465]."

Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer

Phase I/II Trial of Pembrolizumab and Androgen-receptor 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 | Trial completion date: Jun 2028 ➔ Dec 2029 | Trial primary completion date: Jun 2026 ➔ Oct 2027

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

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

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