Anti-tumour Activity of (177Lu) rhPSMA-10.1 Injection
Study Details
Study Description
Brief Summary
To determine the dose, safety, radiation dosimetry and efficacy of 177Lu-rhPSMA-10.1 in participants with PSMA-expressing metastatic castrate resistant prostate cancer.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Detailed Description
This is an interventional, non-randomised, open-label, integrated Phase 1 & 2 study to assess the safety, radiation dosing regimen and anti-tumour activity of Lutetium (177Lu) rhPSMA-10.1 (Tx IMP) in men with metastatic castrate-resistant prostate cancer (mCRPC). The study will consist of 2 parts: a Phase 1, with safety, dose-finding, and dosimetry components, and a Phase 2, with assessment of efficacy and safety utilising the dose selected from Phase 1. Both phases will include subjects with prostate-specific membrane antigen (PSMA)-positive mCRPC as detected using 18F-rhPSMA-7.3 diagnostic IMP.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Phase 1, Cohort A Subjects with PSMA positive disease will receive 5.55GBq of 177Lu-rhPSMA-10.1 (maximum of 3 cycles). |
Drug: 177Lu-rhPSMA-10.1 injection
Therapeutic cycles of 177Lu-rhPSMA-10.1
Other Names:
Diagnostic Test: 18F-rhPSMA-7.3 injection
18F-rhPSMA-7.3 at an administered activity of 296 MBq (8 mCi) for PET/CT scan to ascertain whether the subject has PSMA-positive disease.
Other Names:
|
Experimental: Phase 1, Cohort B Subjects with PSMA positive disease will receive 7.4GBq of 177Lu-rhPSMA-10.1 (maximum of 2 cycles). |
Drug: 177Lu-rhPSMA-10.1 injection
Therapeutic cycles of 177Lu-rhPSMA-10.1
Other Names:
Diagnostic Test: 18F-rhPSMA-7.3 injection
18F-rhPSMA-7.3 at an administered activity of 296 MBq (8 mCi) for PET/CT scan to ascertain whether the subject has PSMA-positive disease.
Other Names:
|
Experimental: Phase 2, Cohort 1, post-chemotherapy mCRPC Subjects with PSMA positive disease will receive up to 6 cycles of the Therapeutic IMP at the Recommended Phase 2 dose [RP2D] |
Drug: 177Lu-rhPSMA-10.1 injection
Therapeutic cycles of 177Lu-rhPSMA-10.1
Other Names:
Diagnostic Test: 18F-rhPSMA-7.3 injection
18F-rhPSMA-7.3 at an administered activity of 296 MBq (8 mCi) for PET/CT scan to ascertain whether the subject has PSMA-positive disease.
Other Names:
|
Experimental: Phase 2, Cohort 2, Taxane-naïve mCRPC Subjects with PSMA positive disease will receive up to 6 cycles of the Therapeutic IMP at the Recommended Phase 2 dose [RP2D] . |
Drug: 177Lu-rhPSMA-10.1 injection
Therapeutic cycles of 177Lu-rhPSMA-10.1
Other Names:
Diagnostic Test: 18F-rhPSMA-7.3 injection
18F-rhPSMA-7.3 at an administered activity of 296 MBq (8 mCi) for PET/CT scan to ascertain whether the subject has PSMA-positive disease.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Phase 1 Incidence of DLTs [6 weeks post final IMP]
Incidence of DLTs during the DLT observation period.
- Phase 1 Frequency and nature of TEAEs [End of study]
Frequency and nature of treatment-emergent adverse events (TEAEs).
- Phase 2, anti-tumour response [12 weekly intervals]
The number of subjects with an anti-tumour response defined as ≥50% reduction in PSA level from baseline.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male subjects, 18 years of age or older with histologically confirmed adenocarcinoma of the prostate.
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Serum testosterone levels <50 ng/dL (1.73 nmol/L) after surgical or continued chemical castration.
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Presence of disease target or non target lesions (per RECIST v1.1) on CT/MRI and full body 99mTc bone scan performed within 28 days of screening.
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Positive disease expression of PSMA as confirmed on PSMA PET/CT scan.
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At least 4 weeks or 5 half-lives (whichever is longer) elapsed between last anti-cancer treatment administration and the initiation of study treatment (except for Luteinising Hormone-releasing Hormone or GnRH).
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Resolution of all previous treatment related toxicities to CTCAE version 5.0 grade of ≤1 (except for chemotherapy induced alopecia and grade 2 peripheral neuropathy or grade 2 urinary frequency which are allowed).
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Prior major surgery must be at least 12 weeks prior to study entry.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 with a life expectancy ≥6 months.
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Adequate bone marrow reserve and organ function as demonstrated by blood count, and serum biochemistry at baseline.
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Adequate contraception for patients and their partners.
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Cohorts:
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Phase 1 and Phase 2 post-chemotherapy mCRPC
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Phase 2 taxane-naïve mCRPC
Exclusion Criteria:
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Known hypersensitivity to the therapeutic or diagnostic IMP or any of its constituents.
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Presence of significant PSMA-negative disease on ceCT/MRI scan
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Diffuse marrow infiltration of disease ('superscan' appearance on full body 99mTc bone scan).
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Symptomatic spinal cord compression, or clinical or radiological findings that are indicative of impending spinal cord compression.
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Known history of haematological malignancy.
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Known history of central nervous system (CNS) metastases.
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Histological findings consistent with neuroendocrine phenotype of prostate cancer.
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Known history of other solid malignancy that may reduce life expectancy and/or may interfere with disease assessment.
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Unresolved urinary tract obstruction defined as radiographic evidence of hydronephrosis with or without ureteric stent/nephrostomy.
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Any uncontrolled significant medical, psychiatric, or surgical condition or laboratory finding that would pose a risk to subject safety or interfere with study participation or interpretation of individual subject results.
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Ongoing treatment with bisphosphonates for bone-targeted therapy.
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Severe urinary incontinence that would preclude safe disposal of radioactive urine.
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Single kidney or renal transplant or any concomitant nephrotoxic therapy that might put the subject at high risk of renal toxicity during the study in the judgement of the investigator.
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Clinically significant abnormalities on a single 12 lead electrocardiogram (ECG) at screening.
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Previously received external beam irradiation to a field that includes more than 30% of the bone marrow or kidneys.
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Previous treatment with any of the following: PSMA targeted radionuclide therapy, Strontium-89, Samarium-153, Rhenium 186, Rhenium-188, Radium-223, hemi-body irradiation.
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Subjects with bilateral hip replacements or any significant metallic implants or objects, that may affect image quality and/or dosimetry calculations.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Advanced Molecular Imaging and Therapy | Glen Burnie | Maryland | United States | 21061 |
Sponsors and Collaborators
- Blue Earth Therapeutics Ltd
- PSI CRO
Investigators
- Study Director: Blue Earth Therapeutics, Blue Earth Therapeutics
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- BET-PSMA-121