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

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: Ac-225 Rosopatamab Tetraxetan (CONV01-α) in Patients (Pts) with Androgen Pathway Modulator Resistant Prostate Cancer (APMR) (ESMO 2026) - No abstract available

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

A phase I dose-escalation/expansion study of fractionated-dose and multiple cycle anti-PSMA-targeted alpha emitter 225Ac-J591 in patients with prostate cancer. (PubMed, Clin Cancer Res) - "Fractionated dosing of 225Ac-J591 appears promising. Further investigation is underway."

Journal • P1 data • Genito-urinary Cancer • Hematological Disorders • Neutropenia • Oncology • Prostate Cancer • Solid Tumor • Thrombocytopenia • Xerostomia

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

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 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

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 part 3: Ac-225 rosopatamab tetraxetan (CONV01-α) in Lu-PSMA-pretreated metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2026) - P2 | "This phase 2 Convergent Therapeutics-sponsored multi-center CONVERGE-01 trial is evaluating the safety and efficacy of CONV01-α in pts with mCRPC, including those previously treated with Lu-PSMA-617 or -I&T (Lu-PSMA), in a dose-escalation (DE) and in an Initial Expansion (IE) cohort. CONV01-ɑ at the RP2D of DL45 is well-tolerated and shows promising activity in a heavily pretreated and Lu-PSMA-exposed population where there are limited therapeutic options available. Subsequent Expansion continues for pts exposed to Lu-PSMA (Part 3) at RP2D of DL45. A pivotal study is planned."

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

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

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

CONVERGE-01: Study Evaluating Dosimetry, Randomized Dose Optimization, Dose Escalation and Efficacy of Ac-225 Rosopatamab Tetraxetan in Participants With PSMA PET-Positive Castration-Resistant Prostate Cancer (CRPC) (clinicaltrials.gov) - P2 | N=93 | Recruiting | Sponsor: Convergent Therapeutics | N=60 ➔ 93 | Trial primary completion date: Dec 2025 ➔ Apr 2027

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

Phase I Study of 225Ac-J591 Plus 177Lu-PSMA Small Molecule for Progressive Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Weill Medical College of Cornell University | N=20 ➔ 42 | Active, not recruiting ➔ Recruiting

Enrollment change • Enrollment open • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • CTCs

Convergent Therapeutics Announces Positive Phase 2 Data at ASCO 2026 Showing Promising Anti-Tumor Activity, Durability, and Favorable Tolerability for CONV01-α in Lu-PSMA-Exposed Metastatic Castration-Resistant Prostate Cancer (mCRPC) (Businesswire) - "This interim dataset from Part 3 of CONVERGE-01 reflects 35 patients with progressive mCRPC previously treated with Lu-177-PSMA radioligand therapy....Median rPFS was 8.4 months in the target dose range in a Lu-PSMA-exposed patient population. Among 25 patients evaluable for PSA response, 40% experienced a PSA decline of ≥50% with similar declines across dose groups and among the patients resistant to Lu-PSMA. No dose-limiting toxicities were observed at any dose level. No treatment-related adverse events led to treatment discontinuation."

P2 data • Castration-Resistant Prostate Cancer

Convergent Therapeutics to Present Largest Set of Prospective Phase 2 Data for an Alpha Radiopharmaceutical in Lu-PSMA-Exposed Metastatic Castration-Resistant Prostate Cancer at ASCO 2026 (Businesswire) - "The June 1 oral presentation of data from CONVERGE-01 study of CONV01-α will highlight antitumor activity, tolerability and emerging durability in patients whose tumors have progressed following Lu-177-PSMA therapy, a growing population with no established standard of care...The tolerability profile includes clinically manageable hematopoietic toxicity, with no renal toxicity and no high-grade xerostomia...Ac-225 supply and manufacturing infrastructure are in place to support late-stage development...Based on the totality of the CONVERGE-01 data, Convergent is planning a pivotal Phase 3 study of CONV01-α in Lu-PSMA-exposed mCRPC patients beginning in mid 2027."

New P3 trial • P2 data • Castration-Resistant 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=52 | Recruiting | Sponsor: Weill Medical College of Cornell University | Active, not recruiting ➔ Recruiting | N=37 ➔ 52

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

Fractionated (dose dense) and multiple dose PSMA-targeted alpha emitter 225Ac-J591 for advanced prostate cancer: Final primary and secondary outcomes (AACR 2026) - P2 | "225Ac-J591 administered in a fractionated (dose-dense) regimen has demonstrated safety with preliminary efficacy. Multiple doses q6 weeks not recommended given timing of blood count nadir, delaying subsequent cycles. Pain may be improved with treatment and overall quality of life stabilizes despite AEs."

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

Convergent Therapeutics to Present Phase 2 Data for CONV01-α in Lu-PSMA pretreated Metastatic Castration-Resistant Prostate Cancer Patients at the 2026 ASCO Annual Meeting (PharmiWeb) - "The oral presentation, scheduled for June 1 in Chicago, will highlight data from patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with Lu-177 PSMA radioligand therapy."

P2 data • Castration-Resistant Prostate Cancer

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 • Oncology • Prostate Cancer • BRCA2 • CHEK2 • MSH2 • TP53

Phase I Study of 225Ac-J591 Plus 177Lu-PSMA Small Molecule for Progressive Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Weill Medical College of Cornell University | Suspended ➔ Active, not recruiting | Phase classification: P1/2 ➔ P1 | N=48 ➔ 20 | Trial completion date: Dec 2027 ➔ Dec 2029 | Trial primary completion date: Dec 2026 ➔ Dec 2027

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

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 | "Prior therapies: ≥2 ARPI in 32 (53%), chemotherapy in 43 (72%), radium-223 in 7 (12%), sipuleucel-T in 17 (34%), and 177Lu-PSMA in 11 (18%). 225Ac-J591 was well tolerated with preserved HRQoL, particularly in the fractionated regimen. FACT-P demonstrated maintained or modest improvement in QoL, while FACT-RNT confirmed stability of treatment-related symptom burden across dose levels. Together, these results suggest that 225Ac-J591 preserves quality of life during therapy without significant physical or emotional decline."

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

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

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