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

Eligibility Criteria

Sex

MALE

Age

18 Years - N/A

Healthy Volunteers

Not accepted

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.
• 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.
• 45 kBq/kg or equivalent fixed dose activity 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.
• 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.
• Single dose 22 kBq/kg or equivalent fixed dose activity Ac-225 rosopatamab tetraxetan — BIOLOGICAL
  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 — BIOLOGICAL
  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 — BIOLOGICAL
  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 — 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.
• 60 kBq/kg or equivalent fixed dose activity 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.

Study Details

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.

Key Dates

First listed

Aug 12, 2024

Start date

Aug 6, 2024

Status verified

Jul 2026

Primary completion

Apr 20, 2027

Completion

Apr 20, 2027

Study Design

Enrollment

93 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

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.

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 ]

Central Contacts

• Study Director
  CONVERGE01
  [email protected]

Locations (9)

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