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)

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

Interventions

BIOLOGICAL

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.

BIOLOGICAL

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.

BIOLOGICAL

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.

BIOLOGICAL

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.

BIOLOGICAL

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.

BIOLOGICAL

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.

BIOLOGICAL

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.

BIOLOGICAL

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.

BIOLOGICAL

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.

Sponsors & Collaborators

• Convergent Therapeutics

  lead INDUSTRY

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

MALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-08-06

Primary Completion

2027-04-20

Completion

2027-04-20

FDA Drug

Yes

Countries

• United States

Study Locations