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 Number: NCT06549465
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: PSMA PET-Positive Castration-Resistant Prostate Cancer
Interventions: BIOLOGICAL: In-111 rosopatamab tetraxetan|BIOLOGICAL: 45 KBq/kg Ac-225 rosopatamab tetraxetan|BIOLOGICAL: 55 KBq/kg Ac-225 rosopatamab tetraxetan|BIOLOGICAL: 60 KBq/kg Ac-225 rosopatamab tetraxetan
Sponsor: Convergent Therapeutics
Sex: MALE
Age: ADULT, OLDER_ADULT
Enrollment: 47
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08
Completion Date: 2027-04
Locations: X Cancer Omaha / Urology Cancer Center, Omaha, Nebraska, 68130-5606, United States

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.

Primary Outcome Measures: 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 Outcome Measures: 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 7|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)|Part 3: Determine the clearance of rosopatamab tetraxetan and Ac-225 rosopatamab tetraxetan from the circulation via measurement in the serum at specified serial timepoints, Through Week 8|Part 3: Radioactivity levels of Ac-225 rosopatamab tetraxetan, Through Day 21