Ac-225 Rosopatamab Tetraxetan for Prostate Cancer

Recruiting at 9 trial locations

Overseen By Study Director

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Convergent Therapeutics

Must be taking: ADT, ARSI

Must not be taking: PARP inhibitors, Anticoagulants

Disqualifiers: Superscans, Prior platinum chemotherapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for advanced prostate cancer that has spread to other parts of the body. It focuses on a radioantibody called Ac-225 rosopatamab tetraxetan, designed to target cancer cells. The study consists of three parts to test the treatment's safety and effectiveness at different doses. Men with prostate cancer that has progressed despite standard treatments, and who may have already tried certain therapies, might be suitable for this trial. Participants will undergo regular check-ups, including blood tests and imaging, to monitor the treatment's effects. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on anti-coagulants or anti-platelet drugs, you may need to stop if your platelet count drops below a certain level.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Ac-225 rosopatamab tetraxetan has been tested in people with prostate cancer and appears safe. In earlier studies, patients who received this treatment tolerated it well, experiencing manageable side effects. Some patients reported mild to moderate tiredness and dry mouth, but these effects did not necessitate stopping the treatment.

The studies also aimed to determine the optimal dose that is both effective and safe. This ensures patients receive a dose potent enough to combat cancer while minimizing serious side effects.

Overall, early results suggest that Ac-225 rosopatamab tetraxetan is a promising treatment for prostate cancer, with a safety profile that supports further research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for prostate cancer, which often include hormone therapy, chemotherapy, and radiotherapy, Ac-225 Rosopatamab Tetraxetan is a novel approach that uses targeted radioligand therapy. This treatment is unique because it employs a radioactive particle, Ac-225, to deliver radiation directly to prostate cancer cells, minimizing damage to surrounding healthy tissue. Researchers are excited about this treatment because it could offer a more precise option with potentially fewer side effects. Additionally, its ability to target cancer cells that have already been treated with Lu-177-PSMA radioligand therapy suggests it could be effective for patients who have limited options due to prior treatments.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that Ac-225 rosopatamab tetraxetan, the investigational treatment in this trial, may help treat prostate cancer. In earlier studies, this treatment significantly reduced prostate-specific antigen (PSA) levels, a marker for cancer activity. Specifically, 46.9% of patients experienced at least a 50% reduction in PSA levels. Another study found that 94% of patients had lower PSA levels, with 64% seeing a 50% reduction and 28% seeing a 90% reduction. These findings suggest the treatment might effectively control cancer growth and reduce tumor activity in prostate cancer patients. Participants in this trial will receive different doses of Ac-225 rosopatamab tetraxetan to evaluate its effectiveness and safety. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with PSMA PET-positive castration-resistant prostate cancer. Participants must have a specific type of advanced prostate cancer and may be sorted into different parts of the study based on their previous treatments. Those who've had Lu-177-PSMA therapy go to Part 3, while others may enter Part 2.

Inclusion Criteria

PSMA PET-positive disease with specific criteria

My cancer has spread to other parts of my body, confirmed by imaging tests.

I have previously received Lu-177-PSMA therapy.

Exclusion Criteria

My bone scan shows extensive cancer spread.

I have never taken PARP inhibitors before.

I have received platinum-based chemotherapy before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dosimetry

One administration of In-111-rosopatamab tetraxetan to characterize the biodistribution of the radioantibody to target organs and prostate cancer lesions

1 week

1 visit (in-person)

Dose Optimization

Participants receive Ac-225 rosopatamab tetraxetan in a single fractionated cycle at either 45 or 60 kBq/Kg

2 weeks

2 visits (in-person)

Dose Escalation and Expansion

Participants receive Ac-225 rosopatamab tetraxetan in a single fractionated cycle at 45, 55, or 60 kBq/Kg, with monitoring for dose limiting toxicities

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ac-225 Rosopatamab Tetraxetan

Trial Overview The study tests a radioantibody called rosopatamab tetraxetan, linked to radioactive elements In-111 or Ac-225. It's given in varying doses to see how well it targets cancer cells and what dose is best tolerated. The trial includes initial dosimetry, randomized dose optimization between two levels (55 or 60 KBq/kg), and dose escalation starting at 45 KBq/kg.

How Is the Trial Designed?

Group I: Part 3: Dose Escalation and Expansion Experimental Treatment 3 Interventions

Participants previously treated with Lu-177-PSMA-radioligand therapy will be assigned to receive one of the three dose levels (45 kBq/kg, 55 kBq/kg, or 60 kBq/kg) depending on the dose limiting toxicities (DLTs) observed.

Group II: Part 2: 60 kBq/kg Ac-225 rosopatamab tetraxetan Experimental Treatment 1 Intervention

Group III: Part 2: 45 kBq/kg Ac-225 rosopatamab tetraxetan Experimental Treatment 1 Intervention

Group IV: Part 1: 148 ± 37 MBq In-111 rosopatamab tetraxetan Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Convergent Therapeutics

Lead Sponsor

Trials

1

Recruited

50+

Published Research Related to This Trial

The study presents an optimized protocol for preparing Ac-225 labeled with PSMA-617, achieving a high yield of 85%-87% and radiochemical purity of 97%-99%, which is crucial for effective targeted alpha therapy in prostate cancer.

This method allows for a single-step, routine in-house radiolabeling process, making it a practical approach for delivering targeted treatment to patients with metastatic castration-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In-House Preparation and Quality Control of Ac-225 Prostate-Specific Membrane Antigen-617 for the Targeted Alpha Therapy of Castration-Resistant Prostate Carcinoma. Thakral, P., Simecek, J., Marx, S., et al.[2022]

The novel radioligand [225Ac]Ac-SibuDAB demonstrated significantly enhanced therapeutic efficacy in treating PSMA-positive tumor xenografts compared to [225Ac]Ac-PSMA-617, requiring only 5 kBq per mouse to eradicate tumors, while [225Ac]Ac-PSMA-617 led to tumor regrowth in treated mice.

[225Ac]Ac-SibuDAB showed improved blood retention and binding to serum albumin, which may contribute to its effectiveness, and was well tolerated at a dose of 30 kBq per mouse, indicating a favorable safety profile for targeted α-therapy in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[225Ac]Ac-SibuDAB for Targeted Alpha Therapy of Prostate Cancer: Preclinical Evaluation and Comparison with [225Ac]Ac-PSMA-617. Busslinger, SD., Tschan, VJ., Richard, OK., et al.[2022]

Lutetium Lu 177 vipivotide tetraxetan (PLUVICTO™) is a targeted radioligand therapy approved in the USA for treating metastatic castration-resistant prostate cancer (mCRPC) that expresses prostate-specific membrane antigen (PSMA), based on positive results from the phase 3 VISION trial.

This therapy specifically targets PSMA, which is overexpressed in prostate cancer cells, allowing for a more effective treatment option for patients who have already undergone other therapies like androgen receptor inhibition and taxane-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 Vipivotide Tetraxetan: First Approval. Keam, SJ.[2022]

In a study of 11 heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC), treatment with Actinium-225 (225Ac) labeled PSMA-617 led to a significant improvement in quality of life, as measured by the NCCN-FACT-FPSI-17 questionnaire, particularly in physical and emotional symptoms.

The therapy resulted in a notable biochemical response, with 46% of patients experiencing a significant decline in Prostate Specific Antigen (PSA) levels, while the treatment was associated with manageable side effects, including some Grade 3 toxicities in a small number of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality-of-Life Outcomes with Actinium-225-Prostate-Specific Membrane Antigen-617 Therapy in Patients with Heavily Pretreated Metastatic Castration-Resistant Prostate Cancer. Satapathy, S., Mittal, BR., Sood, A., et al.[2022]

Actinium-225 (Ac-225) PSMA radioligand therapy (RLT) shows promising efficacy in treating metastatic castration-resistant prostate cancer (mCRPC), with 81% of patients experiencing a decline in PSA levels and 60% achieving more than a 50% reduction.

The treatment is generally safe, with the most common side effect being mild to moderate xerostomia (dry mouth) reported in 73.9% of patients, indicating that Ac-225 may have fewer severe side effects compared to traditional beta-emitting therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Actinium-225 Prostate-Specific Membrane Antigen Radioligand Therapy in Metastatic Prostate Cancer: A Systematic Review and Metanalysis. Parida, GK., Panda, RA., Bishnoi, K., et al.[2023]

PSMA-targeted thorium-227 conjugate (PSMA-TTC) effectively targets and induces DNA damage in prostate cancer cells, leading to cell death, particularly in cells with high PSMA expression.

In preclinical models, PSMA-TTC demonstrated strong antitumor efficacy, significantly reducing tumor growth and abnormal bone growth associated with metastatic prostate cancer, supporting its potential for clinical evaluation in ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Efficacy of a PSMA-Targeted Thorium-227 Conjugate (PSMA-TTC), a Targeted Alpha Therapy for Prostate Cancer. Hammer, S., Hagemann, UB., Zitzmann-Kolbe, S., et al.[2021]

The study of 32 patients with metastatic castration-resistant prostate cancer (mCRPC) showed that the radiolabeled antibody 225Ac-J591 is safe, with a maximum tolerated dose not reached and only one patient experiencing dose-limiting toxicity.

Preliminary efficacy results indicated that 46.9% of patients had at least a 50% decline in prostate-specific antigen (PSA) levels, and 59.1% showed a response in circulating tumor cell counts, suggesting potential effectiveness of this novel therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate-Specific Membrane Antigen-Targeting Alpha Emitter via Antibody Delivery for Metastatic Castration-Resistant Prostate Cancer: A Phase I Dose-Escalation Study of 225Ac-J591. Tagawa, ST., Thomas, C., Sartor, AO., et al.[2023]

The FDA has approved 177Lu-PSMA-617 for treating advanced metastatic castrate-resistant prostate cancer (mCRPC), marking a significant advancement in PSMA-targeted therapies.

Various PSMA-targeted radiopharmaceuticals, including both beta and alpha emitters, are in development, with promising results for alpha therapies like 225Ac-PSMA-617, although there are concerns about potential toxicity to salivary and renal tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate specific membrane antigen binding radiopharmaceuticals: Current data and new concepts. Sartor, O., Baghian, A.[2022]

In a meta-analysis of 263 patients with metastatic castration-resistant prostate cancer (mCRPC), 225Ac-PSMA radioligand therapy (RLT) resulted in over 60% of patients experiencing more than a 50% decline in prostate-specific antigen (PSA) levels, indicating significant therapeutic efficacy.

While 225Ac-PSMA RLT showed promising results, common adverse effects included xerostomia (dry mouth) in about 63% of patients and severe hematotoxicity (anemia, leukocytopenia, and thrombocytopenia) in 4% to 14% of patients, highlighting the need for monitoring side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of 225Ac-Labeled Prostate-Specific Membrane Antigen Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis. Lee, DY., Kim, YI.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS289

CONVERGE-01: Dosimetry, randomized dose optimization, ... Ac-225 rosopatamab tetraxetan (CONV01-ɑ, formerly Ac-225-J591) has been evaluated for safety and efficacy in sequential investigator-initiated ...

2. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-prostate-cancer/158312-asco-gu-2025-converge-01-dosimetry-randomized-dose-optimization-dose-escalation-and-efficacy-of-ac-225-rosopatamab-tetraxetan-in-participants-with-psma-positive-crpc.html

ASCO GU 2025: CONVERGE-01: Dosimetry, Randomized ... This drug is not unfamiliar to the prostate cancer community, Ac-225 rosopatamab tetraxetan (CONV01-ɑ, formerly Ac-225-J591) has been ...

3. convergentrx.com convergentrx.com/publications/

Scientific Publications Learn about CONV01-α (formerly Ac-225-J591), which is an alpha-emitting radioantibody with a promising clinical future in mCRPC.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37922438/

A Phase I Dose-Escalation Study of 225Ac-J591 - PubMed - NIH Prostate-specific antigen (PSA) declines and circulating tumor cell (CTC) control were observed: 46.9% had at least 50% PSA decline at any time ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT04886986

Phase I/II 225Ac-J591 Plus 177Lu-PSMA-I&T for ... 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06549465

NCT06549465 | Study Evaluating Dosimetry, Randomized ... This is a three-part study evaluating the safety and efficacy of a PSMA-directed radioantibody (rosopatamab tetraxetan, conjugated to either In-111 or ...

7. synapse.patsnap.com synapse.patsnap.com/drug/75d7ff5b83c3422687bd15c0383cd6a1

Actinium 225-J591 - Drug Targets, Indications, Patents PURPOSE: Novel therapies are needed to extend survival in metastatic castration-resistant prostate cancer (mCRPC). · METHODS: · RESULTS: · CONCLUSION:.