Recruiting
Phase 2

Ac-225 Rosopatamab

Sponsor:

Convergent Therapeutics

Code:

NCT06549465

Conditions

PSMA PET-Positive Castration-Resistant Prostate Cancer

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Interventions

In-111 rosopatamab tetraxetan

45 kBq/kg Ac-225 rosopatamab tetraxetan

45 kBq/kg or equivalent fixed dose activity Ac-225 rosopatamab tetraxetan

60 kBq/kg Ac-225 rosopatamab tetraxetan

Single dose 22 kBq/kg or equivalent fixed dose activity Ac-225 rosopatamab tetraxetan

Study Details

Brief summary:

This is a four-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. Part 4 will be an extended regimen in dose escalation and expansion. 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 qualifying for Part 4 will initially receive two doses (dose administration on Day 1 and Day 15) at the dose level selected in Part 2, followed by a single third dose of Ac-225 rosopatamab tetraxetan administered approximately 12 weeks after completion of the Part 2 fractionated dosing regimen. The starting dose level for Part 4 will be 22 kBq/kg (or fixed activity equivalent). Dose limiting toxicities (DLTs) will be monitored following administration of the third dose in Part 4 to determine the recommended phase 2 dose (RP2D) of a third dose of Ac-225 rosopatamab tetraxetan. 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 ID

NCT06549465

Start date

Aug 6, 2024

Status verified date

Jul, 2026

Completion date

Apr 20, 2027

Anticipated

Primary completion date

Apr 20, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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

1. Serum PSA progression as defined by PCWG3 (rising PSA consisting of two consecutive increases measured at least 3 weeks apart, of a rise of >25%, and with an absolute rise of 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, 3, and 4: 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, 2, and 4 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 administration of Ac-225 rosopatamab tetraxetan.
  • 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 and 4 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, except for bispecific or CAR-T therapies

Part 3 Only:

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

Study Design

Enrollment

93 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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

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

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

experimental: 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, or equivalent fixed dose activity) depending on the dose limiting toxicities (DLTs) observed.

experimental: Part 4: Dose Escalation and Expansion

Participants will initially receive two doses of the Part 2 selected dose level, followed by a single third dose of Ac-225 rosopatamab tetraxetan approximately 12 weeks after the completion of the Part 2 fractionated dosing regimen. Participants will be assigned to receive one of the three dose levels (22 kBq/kg, 34 kBq/kg, or 45 kBq/kg, or equivalent fixed dose activity) depending on the dose limiting toxicities (DLTs) observed.

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.

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.

45 kBq/kg or equivalent fixed dose activity 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.

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.

Single dose 22 kBq/kg or equivalent fixed dose activity Ac-225 rosopatamab tetraxetan

22 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. A single dose will be given.

Single dose 34 kBq/kg or equivalent fixed dose activity Ac-225 rosopatamab tetraxetan

34 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. A single dose will be given.

Single dose 45 kBq/kg or equivalent fixed dose activity Ac-225 rosopatamab tetraxetan

45 kBq/kg Ac-225 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes. A single dose will be given.

55 kBq/kg or equivalent fixed dose activity 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.

60 kBq/kg or equivalent fixed dose activity 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.

Primary outcome measure

  • 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 [ Time Frame: 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 [ Time Frame: Screening through Week 12 ]
  • Part 2: Proportion of participants who achieve a greater than or equal to 50% decline in prostate-specific antigen (PSA50) [ Time Frame: 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 [ Time Frame: Screening through Week 12 ]
  • Part 3: Determine the recommended Phase 2 dose (RP2D) of Ac-225 rosopatamab tetraxetan [ Time Frame: 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) [ Time Frame: Through end of study (approximately 3 years) or until PSA progression as defined by PCWG3 criteria ]
  • Part 4: Incidence of AEs and SAEs overall, by severity, by relationship to study drug, and leading to discontinuation of study intervention [ Time Frame: Screening through Week 12 ]
  • Part 4: Determine the recommended Phase 2 dose (RP2D) of Ac-225 rosopatamab tetraxetan [ Time Frame: Through end of study (approximately 3 years) ]

Central Contacts and Locations

Central contacts

Study Director

CONVERGE01CONVERGE01@convergentrx.com

Locations

University of California San Diego

Recruiting

San Diego, California, United States, 92093

Principal Investigator:

Rana McKay, MD

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Principal Investigator:

Praful Ravi, MB, BChir, MRCP

Washington University in St. Louis

Recruiting

St Louis, Missouri, United States, 63130

Principal Investigator:

Vikas Prasad, MD, PhD

X Cancer Omaha / Urology Cancer Center

Recruiting

Omaha, Nebraska, United States, 68130-5606

Principal Investigator:

Luke Nordquist, MD

Laura & Isaac Perlmutter Cancer Center

Recruiting

New York, New York, United States, 10016

Principal Investigator:

David Wise, MD

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Principal Investigator:

Anis Hamid, MD

New York Presbyterian/Weill Cornell Medical Center

Recruiting

New York, New York, United States, 10065

Principal Investigator:

Cora Sternberg, MD

Duke University Medical Center

Recruiting

Durham, North Carolina, United States, 27710

Principal Investigator:

Daniel George, MD

The Cleveland Clinic Foundation

Recruiting

Cleveland, Ohio, United States, 44195

Principal Investigator:

Shilpa Gupta, MD

More Information

Sponsor

Convergent Therapeutics

Last update posted

Jul 20, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Convergent Therapeutics on 2026-07-20.