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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)

ConditionPSMA PET-Positive Castration-Resistant Prostate Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexMale
Age18+
SponsorConvergent Therapeutics

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Serum PSA progression consisting of two consecutive increases in PSA measured at least 1 week apart. The minimal study baseline value is 2.0 ng/mL

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)

Progression of bone disease defined by PCWG3 as evaluable disease or new bone lesions by bone scan

Identification of new soft tissue or bone lesions on PSMA PET imaging

Disqualifiers

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)

Trial design

Design model

Sequential

Treatments tested in this trial

  • In-111 rosopatamab tetraxetan

    Biological/Vaccine

    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/Vaccine

    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.

  • 55 kBq/kg Ac-225 rosopatamab tetraxetan

    Biological/Vaccine

    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 Ac-225 rosopatamab tetraxetan

    Biological/Vaccine

    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.

Treatment groups

60 Participants
are divided into 4 treatment groups
Group A: Part 1: 148 ± 37 MBq In-111 rosopatamab tetraxetanExperimental treatment 1 intervention
Group B: Part 2: 45 kBq/kg Ac-225 rosopatamab tetraxetanExperimental treatment 1 intervention
Group C: Part 2: 60 kBq/kg Ac-225 rosopatamab tetraxetanExperimental treatment 1 intervention
Group D: Part 3: Dose Escalation and ExpansionExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

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
2

Part 2: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) overall, by severity, and leading to discontinuation of study intervention

Time frame
Screening through Week 12
3

Part 2: Proportion of participants who achieve a greater than or equal to 50% decline in prostate-specific antigen (PSA50)

Time frame
Through end of study (approximately 3 years) or until PSA progression as defined by PCWG3 criteria
4

Part 3: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) overall, by severity, and leading to discontinuation of study intervention

Time frame
Screening through Week 12

Secondary outcomes

1

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

Time frame
Through Week 8
2

Part 2: Radioactivity levels of Ac-225 rosopatamab tetraxetan

Time frame
Through Day 21
3

Part 2: Radiation dosimetry of Ac-225 rosopatamab tetraxetan: Absorbed radiation dose (expressed as Gy/MBq) in normal organs

Time frame
Day 1 through Day 15
4

Part 2: Biochemical progression-free survival (bPFS) as assessed by the Prostate Cancer Working Group 3 (PCWG3)

Time frame
Through end of study (approximately 3 years) or until disease progression

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Convergent Therapeutics

Lead sponsor

Source ClinicalTrials.gov
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