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)

NCT ID: NCT06549465

Last Updated: 2025-08-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-06
• Study Completion Date: 2027-04-30

Brief Summary

This is a three-part study evaluating the safety and efficacy of a PSMA-directed radioantibody (rosopatamab tetraxetan, conjugated to either In-111 or Ac-225). Part 1 will consist of one administration of In-111-rosopatamab tetraxetan to characterize the biodistribution of the radioantibody to target organs and prostate cancer lesions. Participants then will be enrolled into either Part 2 (Dose Optimization) or Part 3 (Dose Escalation and Expansion) depending on their prior treatment history. Participants qualifying for Part 2 will be randomized to receive Ac-225 rosopatamab tetraxetan in a single fractionated cycle (dose administration on Day 1 and Day 15) at either 45 or 60 kBq/Kg. Participants qualifying for Part 3 must have received prior Lu-177-PSMA-radioligand therapy and will receive Ac-225 rosopatamab tetraxetan in a single fractionated cycle at 45, 55, or 60 kBq/Kg. Dose limiting toxicities (DLTs) will be monitored in Part 3 to determine the recommended phase 2 dose (RP2D), and the study may enroll additional participants to be treated with the RP2D dose level. Participants enrolled into any part will attend study visits which will include blood samples, electrocardiogram (ECG), radiographic imaging, and physical examinations along with other assessments.

Conditions

PSMA PET-Positive Castration-Resistant Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: 148 ± 37 MBq In-111 rosopatamab tetraxetan

Group Type: EXPERIMENTAL

In-111 rosopatamab tetraxetan

Intervention Type: BIOLOGICAL

A single dose of 148 ± 37 MBq In-111 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes.

Part 2: 45 kBq/kg Ac-225 rosopatamab tetraxetan

Group Type: EXPERIMENTAL

45 kBq/kg Ac-225 rosopatamab tetraxetan

Intervention Type: BIOLOGICAL

45 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. Doses will be given two weeks apart for a total of two doses.

Part 2: 60 kBq/kg Ac-225 rosopatamab tetraxetan

Group Type: EXPERIMENTAL

60 kBq/kg Ac-225 rosopatamab tetraxetan

Intervention Type: BIOLOGICAL

60 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. Doses will be given two weeks apart for a total of two doses.

Part 3: Dose Escalation and Expansion

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 Type: EXPERIMENTAL

45 kBq/kg Ac-225 rosopatamab tetraxetan

Intervention Type: BIOLOGICAL

45 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. Doses will be given two weeks apart for a total of two doses.

55 kBq/kg Ac-225 rosopatamab tetraxetan

Intervention Type: BIOLOGICAL

55 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. Doses will be given two weeks apart for a total of two doses.

60 kBq/kg Ac-225 rosopatamab tetraxetan

Intervention Type: BIOLOGICAL

60 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. Doses will be given two weeks apart for a total of two doses.

Interventions

In-111 rosopatamab tetraxetan

A single dose of 148 ± 37 MBq In-111 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes.

Intervention Type: BIOLOGICAL

45 kBq/kg Ac-225 rosopatamab tetraxetan

45 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. Doses will be given two weeks apart for a total of two doses.

Intervention Type: BIOLOGICAL

55 kBq/kg Ac-225 rosopatamab tetraxetan

55 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. Doses will be given two weeks apart for a total of two doses.

Intervention Type: BIOLOGICAL

60 kBq/kg Ac-225 rosopatamab tetraxetan

60 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. Doses will be given two weeks apart for a total of two doses.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Progressive CRPC defined as castrate levels of testosterone and progressing by at least one of the following criteria:

1. Serum PSA progression consisting of two consecutive increases in PSA measured at least 1 week apart. The minimal study baseline value is 2.0 ng/mL

2. Soft tissue progression defined as a ≥20% increase in the sum of the diameter (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest sum of the diameter since the previous treatment was started or the appearance of one or more new lesions by CT/magnetic resonance imaging (MRI)

3. Progression of bone disease defined by PCWG3 as evaluable disease or new bone lesions by bone scan

4. Identification of new soft tissue or bone lesions on PSMA PET imaging

• Metastatic disease defined as either or both of the following:

1. Parts 1, 2 and 3: Documented M1 disease on conventional imaging (CT/MRI of the chest/abdomen/pelvis and/or Technetium 99m [99mTc] whole-body bone scan)

2. Parts 1 and 2 only: Identification of bone lesion(s), extra-pelvic soft tissue lesion(s), or visceral metastases on PSMA PET imaging with an FDA-approved imaging agent

• PSMA PET-positive disease, defined as at least one PSMA-positive metastatic lesion and no PSMA-negative lesions
• Progression following treatment with ADT and at least one ARSI (e.g., enzalutamide, apalutamide, darolutamide, and/or abiraterone acetate)
• The standard of care use (in the setting of metastatic CRPC with significant burden of active bone metastases) of antiresorptive bone-targeted agents (e.g., zoledronic acid, denosumab) is required for all participants without a contraindication, for at least 4 weeks prior to study drug administration
• Participants with HIV are eligible if they are well-controlled (i.e, an undetectable HIV viral load (<50 copies/mL) within 6 months of enrollment and a stable ART regimen for at least 6 months prior to enrollment) and at low risk for HIV-related illness

Part 3 Only:

• Prior treatment with Lu-177-PSMA-radioligand therapy
• Prior treatment with up to only one taxane-based chemotherapy regimen is allowed

Exclusion Criteria

• Superscans by nuclear medicine/99mTc bone scan
• A known malignancy that is progressing or has required active treatment within the past 3 years other than CRPC, which is expected to alter life expectancy or may interfere with CRPC disease assessment
• Prior platinum-based chemotherapy
• Prior PARP inhibitors (e.g., olaparib or rucaparib)
• Prior treatment with Radium-223, Actinium-225, Strontium-89, Samarium-153, Rheunium-186, or Rhenium-188
• Participants receiving anti-coagulants or anti-platelet drugs (e.g., aspirin or nonsteroidal anti-inflammatory drugs [NSAIDs]) who cannot discontinue use if platelet count decreases to <50,000

Part 2 Only:

• Prior chemotherapy for CRPC. Prior taxane chemotherapy for HSPC is allowed if discontinued ≥1 year prior to randomization
• Prior radiopharmaceutical therapy (e.g., Ra-223, Lu-177-PSMA-617, or Lu-177-PSMA-I&T)
• Prior PSMA-targeted therapy

Part 3 Only:

• Prior PSMA-targeted therapy (e.g., antibody-drug conjugates or CAR-T therapy), except for Lu-177-PSMA-radioligand therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Convergent Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of California San Diego

San Diego, California, United States

Site Status: RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status: RECRUITING

Washington University in St. Louis

St Louis, Missouri, United States

Site Status: RECRUITING

X Cancer Omaha / Urology Cancer Center

Omaha, Nebraska, United States

Site Status: RECRUITING

Laura & Isaac Perlmutter Cancer Center

New York, New York, United States

Site Status: RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status: RECRUITING

New York Presbyterian/Weill Cornell Medical Center

New York, New York, United States

Site Status: RECRUITING

Duke University Medical Center

Durham, North Carolina, United States

Site Status: RECRUITING

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Study Director

Role: CONTACT

CONVERGE01@convergentrx.com

CONVERGE01

Other Identifiers

CONVERGE-01

Identifier Type: -

Identifier Source: org_study_id