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

Trial Title: 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

NCT ID: NCT06549465

Condition: PSMA PET-Positive Castration-Resistant Prostate Cancer

Conditions: Official terms:
Prostatic Neoplasms
1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Sequential Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: In-111 rosopatamab tetraxetan
Description: A single dose of 148 ± 37 MBq In-111 rosopatamab tetraxetan will be administered as an IV infusion over a period of 10 minutes.
Arm group label: Part 1: 148 ± 37 MBq In-111 rosopatamab tetraxetan

Intervention type: Biological
Intervention name: 45 KBq/kg Ac-225 rosopatamab tetraxetan
Description: 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.
Arm group label: Part 3: Dose Escalation

Intervention type: Biological
Intervention name: 55 KBq/kg Ac-225 rosopatamab tetraxetan
Description: 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.
Arm group label: Part 2: 55 KBq/kg Ac-225 rosopatamab tetraxetan
Arm group label: Part 3: Dose Escalation

Intervention type: Biological
Intervention name: 60 KBq/kg Ac-225 rosopatamab tetraxetan
Description: 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.
Arm group label: Part 2: 60 KBq/kg Ac-225 rosopatamab tetraxetan
Arm group label: Part 3: Dose Escalation

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) 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 55 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.

Criteria for 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 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). Part 3 Only: - Prior treatment with Lu-177-PSMA-radioligand therapy - Prior treatment with one taxane-based chemotherapy is allowed, but not required. 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). - 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.

Gender: Male

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: X Cancer Omaha / Urology Cancer Center

Address:
City: Omaha
Zip: 68130-5606
Country: United States

Status: Recruiting

Contact:
Last name: Dr. Luke Nordquist

Facility:
Name: The Cleveland Clinic Foundation

Address:
City: Cleveland
Zip: 44195
Country: United States

Status: Recruiting

Start date: August 6, 2024

Completion date: April 2027

Lead sponsor:
Agency: Convergent Therapeutics
Agency class: Industry

Source: Convergent Therapeutics

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06549465