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
- Interventions
- Biological: In-111 rosopatamab tetraxetanBiological: 45 kBq/kg Ac-225 rosopatamab tetraxetanBiological: 60 kBq/kg Ac-225 rosopatamab tetraxetanBiological: 55 kBq/kg Ac-225 rosopatamab tetraxetan
- Registration Number
- NCT06549465
- Lead Sponsor
- Convergent Therapeutics
- Brief 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 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 60
-
Progressive CRPC defined as castrate levels of testosterone and progressing by at least one of the following criteria:
- 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
- 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
-
Metastatic disease defined as either or both of the following:
- 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)
- 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)
-
The standard of care use (in the setting of metastatic CRPC) of antiresorptive bone-targeted agents (e.g., zoledronic acid, denosumab) is required for all participants without a contraindication, for at least 4 weeks prior to study drug administration
-
Participants with HIV are eligible if they are well-controlled and at low risk for HIV-related illness
Part 3 Only:
- Prior treatment with Lu-177-PSMA-radioligand therapy
- Prior treatment with only one taxane-based chemotherapy is required
- 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)
- Prior treatment with Radium-223, Actinium-225, Strontium-89, Samarium-153, Rheunium-186, or Rhenium-188
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1: 148 ± 37 MBq In-111 rosopatamab tetraxetan In-111 rosopatamab tetraxetan - Part 2: 45 kBq/kg Ac-225 rosopatamab tetraxetan 45 kBq/kg Ac-225 rosopatamab tetraxetan - Part 2: 60 kBq/kg Ac-225 rosopatamab tetraxetan 60 kBq/kg Ac-225 rosopatamab tetraxetan - Part 3: Dose Escalation and Expansion 45 kBq/kg Ac-225 rosopatamab tetraxetan 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) depending on the dose limiting toxicities (DLTs) observed. Part 3: Dose Escalation and Expansion 55 kBq/kg Ac-225 rosopatamab tetraxetan 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) depending on the dose limiting toxicities (DLTs) observed. Part 3: Dose Escalation and Expansion 60 kBq/kg Ac-225 rosopatamab tetraxetan 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) depending on the dose limiting toxicities (DLTs) observed.
- Primary Outcome Measures
Name Time Method 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: 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 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
- Secondary Outcome Measures
Name Time Method 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 15 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 Week 8
Trial Locations
- Locations (7)
X Cancer Omaha / Urology Cancer Center
🇺🇸Omaha, Nebraska, United States
University of California San Diego
🇺🇸San Diego, California, United States
Washington University in St. Louis
🇺🇸Saint Louis, Missouri, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Laura & Isaac Perlmutter Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States