RECRUITING

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)

Conditions

PSMA PET-Positive Castration-Resistant Prostate Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase 2, Open-label 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

Quick Facts

Study Start:2024-08-06

Study Completion:2027-04

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06549465

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 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) 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 and at low risk for HIV-related illness * Prior treatment with Lu-177-PSMA-radioligand therapy * Prior treatment with only one taxane-based chemotherapy is required	* 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 * 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 * Prior PSMA-targeted therapy (e.g., antibody-drug conjugates or CAR-T therapy), except for Lu-177-PSMA-radioligand therapy

Inclusion Criteria

Exclusion 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 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) 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 and at low risk for HIV-related illness
* Prior treatment with Lu-177-PSMA-radioligand therapy
* Prior treatment with only one taxane-based chemotherapy is required

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

Contacts and Locations

Study Contact

Study Director

CONTACT

CONVERGE01

CONVERGE01@convergentrx.com

Study Locations (Sites)

X Cancer Omaha / Urology Cancer Center

Omaha, Nebraska, 68130-5606

United States

Laura & Isaac Perlmutter Cancer Center

New York, New York, 10016

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195

United States

Collaborators and Investigators

Sponsor: Convergent Therapeutics

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-08-06

Study Completion Date2027-04

Study Record Updates

Study Start Date2024-08-06

Study Completion Date2027-04

Terms related to this study

Additional Relevant MeSH Terms

PSMA PET-Positive Castration-Resistant Prostate Cancer