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)

NCT06549465 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CONVERGE-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 9

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

Outcome Measures

Primary Outcomes (6)

• Part 1: Visual evaluation on whole body planar scans (days 1 and 4) with comparison to reference scans for the presence of radiolabeled rosopatamab textraxetan in organs of interest (e.g., liver, circulation, spleen) to determine biodistribution

  Day 1 and Day 4

• Part 2: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) overall, by severity, and leading to discontinuation of study intervention

  Screening through Week 12

• Part 2: Proportion of participants who achieve a greater than or equal to 50% decline in prostate-specific antigen (PSA50)

  Through end of study (approximately 3 years) or until PSA progression as defined by PCWG3 criteria

• Part 3: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) overall, by severity, and leading to discontinuation of study intervention

  Screening through Week 12

• Part 3: Determine the recommended Phase 2 dose (RP2D) of Ac-225 rosopatamab tetraxetan

  Day 1 through 6 weeks

• Part 3 (Participants treated at RP2D): Proportion of participants who achieve a greater than or equal to 50% decline in prostate-specific antigen (PSA50)

  Through end of study (approximately 3 years) or until PSA progression as defined by PCWG3 criteria

Secondary Outcomes (7)

• Part 2: Determine the clearance of rosopatamab tetraxetan and Ac-225 rosopatamab tetraxetan via measurement of whole blood and serum levels at specified serial timepoints

  Through Week 8

• Part 2: Radioactivity levels of Ac-225 rosopatamab tetraxetan

  Through Day 21

• Part 2: Radiation dosimetry of Ac-225 rosopatamab tetraxetan: Absorbed radiation dose (expressed as Gy/MBq) in normal organs

  Day 1 through Day 15

• Part 2: Biochemical progression-free survival (bPFS) as assessed by the Prostate Cancer Working Group 3 (PCWG3)

  Through end of study (approximately 3 years) or until disease progression

• Part 3: Proportion of participants who achieve PSA50

  Through end of study (approximately 3 years)

Study Arms (4)

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

EXPERIMENTAL

Biological: In-111 rosopatamab tetraxetan

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

EXPERIMENTAL

Biological: 45 kBq/kg Ac-225 rosopatamab tetraxetan

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

EXPERIMENTAL

Biological: 60 kBq/kg Ac-225 rosopatamab tetraxetan

Part 3: Dose Escalation and Expansion

EXPERIMENTAL

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.

Biological: 45 kBq/kg Ac-225 rosopatamab tetraxetan; Biological: 55 kBq/kg Ac-225 rosopatamab tetraxetan; Biological: 60 kBq/kg Ac-225 rosopatamab tetraxetan

Interventions

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

45 kBq/kg Ac-225 rosopatamab tetraxetan 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: 45 kBq/kg Ac-225 rosopatamab tetraxetan; Part 3: Dose Escalation and Expansion

55 kBq/kg Ac-225 rosopatamab tetraxetan 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.

Part 3: Dose Escalation and Expansion

60 kBq/kg Ac-225 rosopatamab tetraxetan 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 2: 60 kBq/kg Ac-225 rosopatamab tetraxetan; Part 3: Dose Escalation and Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Progressive CRPC defined as castrate levels of testosterone and progressing by at least one of the following criteria:
• 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
• 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)
• Progression of bone disease defined by PCWG3 as evaluable disease or new bone lesions by bone scan
• Identification of new soft tissue or bone lesions on PSMA PET imaging
• Metastatic disease defined as either or both of the following:
• 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)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Convergent Therapeutics: lead

Study Sites (9)

University of California San Diego

San Diego, California, 92093, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Washington University in St. Louis

St Louis, Missouri, 63130, United States

RECRUITING

X Cancer Omaha / Urology Cancer Center

Omaha, Nebraska, 68130-5606, United States

RECRUITING

Laura & Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

New York Presbyterian/Weill Cornell Medical Center

New York, New York, 10065, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

RECRUITING

Central Study Contacts

Study Director

CONTACT

CONVERGE01; CONVERGE01@convergentrx.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2024
• First Posted: August 12, 2024
• Study Start: August 6, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): April 1, 2027
• Last Updated: August 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)