Anti-tumour Activity of (177Lu) rhPSMA-10.1 Injection

Sponsor
Blue Earth Therapeutics Ltd (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05413850
Collaborator
PSI CRO (Industry)
150
1
4
51.3
2.9

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
  • Drug: 177Lu-rhPSMA-10.1 injection
  • Diagnostic Test: 18F-rhPSMA-7.3 injection
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

Study Type:
Interventional
Anticipated Enrollment :
150 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Multicentre, Integrated Phase 1 & 2 Study to Evaluate the Safety, Tolerability, Radiation Dosimetry and Anti-tumour Activity of Lutetium (177Lu) rhPSMA-10.1 Injection in Men With Metastatic Castrate-resistant Prostate Cancer
Actual Study Start Date :
Jul 20, 2022
Anticipated Primary Completion Date :
Aug 27, 2026
Anticipated Study Completion Date :
Oct 27, 2026

Arms and Interventions

Arm Intervention/Treatment
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:
  • 177Lu-rhPSMA-10.1
  • 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:
  • 18F-rhPSMA-7.3
  • 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:
  • 177Lu-rhPSMA-10.1
  • 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:
  • 18F-rhPSMA-7.3
  • 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:
  • 177Lu-rhPSMA-10.1
  • 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:
  • 18F-rhPSMA-7.3
  • 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:
  • 177Lu-rhPSMA-10.1
  • 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:
  • 18F-rhPSMA-7.3
  • Outcome Measures

    Primary Outcome Measures

    1. Phase 1 Incidence of DLTs [6 weeks post final IMP]

      Incidence of DLTs during the DLT observation period.

    2. Phase 1 Frequency and nature of TEAEs [End of study]

      Frequency and nature of treatment-emergent adverse events (TEAEs).

    3. 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

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Male subjects, 18 years of age or older with histologically confirmed adenocarcinoma of the prostate.

    2. Serum testosterone levels <50 ng/dL (1.73 nmol/L) after surgical or continued chemical castration.

    3. 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.

    4. Positive disease expression of PSMA as confirmed on PSMA PET/CT scan.

    5. 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).

    6. 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).

    7. Prior major surgery must be at least 12 weeks prior to study entry.

    8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 with a life expectancy ≥6 months.

    9. Adequate bone marrow reserve and organ function as demonstrated by blood count, and serum biochemistry at baseline.

    10. Adequate contraception for patients and their partners.

    11. Cohorts:

    12. Phase 1 and Phase 2 post-chemotherapy mCRPC

    13. Phase 2 taxane-naïve mCRPC

    Exclusion Criteria:
    1. Known hypersensitivity to the therapeutic or diagnostic IMP or any of its constituents.

    2. Presence of significant PSMA-negative disease on ceCT/MRI scan

    3. Diffuse marrow infiltration of disease ('superscan' appearance on full body 99mTc bone scan).

    4. Symptomatic spinal cord compression, or clinical or radiological findings that are indicative of impending spinal cord compression.

    5. Known history of haematological malignancy.

    6. Known history of central nervous system (CNS) metastases.

    7. Histological findings consistent with neuroendocrine phenotype of prostate cancer.

    8. Known history of other solid malignancy that may reduce life expectancy and/or may interfere with disease assessment.

    9. Unresolved urinary tract obstruction defined as radiographic evidence of hydronephrosis with or without ureteric stent/nephrostomy.

    10. 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.

    11. Ongoing treatment with bisphosphonates for bone-targeted therapy.

    12. Severe urinary incontinence that would preclude safe disposal of radioactive urine.

    13. 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.

    14. Clinically significant abnormalities on a single 12 lead electrocardiogram (ECG) at screening.

    15. Previously received external beam irradiation to a field that includes more than 30% of the bone marrow or kidneys.

    16. Previous treatment with any of the following: PSMA targeted radionuclide therapy, Strontium-89, Samarium-153, Rhenium 186, Rhenium-188, Radium-223, hemi-body irradiation.

    17. 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
    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.
    Responsible Party:
    Blue Earth Therapeutics Ltd
    ClinicalTrials.gov Identifier:
    NCT05413850
    Other Study ID Numbers:
    • BET-PSMA-121
    First Posted:
    Jun 10, 2022
    Last Update Posted:
    Jul 28, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Blue Earth Therapeutics Ltd
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 28, 2022