177Lu-DOTA-TLX591 Safety, Biodistribution and Dosimetry Study
Condition: Metastatic Prostate Cancer
MeSH terms: Prostatic Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a Phase 1 trial of TLX591, a monoclonal antibody HuX591 conjugated with a DOTA
      chelator and radiolabelled with 177Lu (177Lu-DOTA-TLX591). TLX591 is being developed as a
      PSMA-targeting antibody to be radiolabelled with a therapeutic radiosotope for the treatment
      of PSMA-expressing tumours, therefore this study has been designed to assess the safety and
      tolerability, pharmacokinetics, whole body biodistribution and radiation dosimetry of
      177Lu-DOTA-TLX591.
    

Detailed description: 
      This multi-center prospective Phase 1 study is designed to evaluate the safety, tolerability,
      biodistribution and dosimetry of 177Lu-DOTA-TLX591 administered to patients together with
      best SoC with metastatic castration-resistant prostate cancer (mCRPC) that expresses PSMA and
      has progressed despite prior treatment with a novel androgen axis drug (NAAD).

      PSMA positivity will be defined by 68Ga-PSMA-11 or [18F]DCFPyL PET/CT where at least one site
      of metastatic disease has an intensity of tracer uptake significantly greater than normal
      liver (i.e., standardized uptake value [SUV]max at least 1.5 times SUV of normal liver.

      Approximately 25-50 eligible patients will be enrolled and evaluated for safety and
      tolerability as well as undergo imaging to allow determination of the biodistribution and
      dosimetry 177Lu-DOTA-TLX591. All patients will receive two single intravenous (IV) infusions
      of 76 mCi each (equivalent to 45 mCi/m2 in a standard 1.7m2 individual) of 177Lu-DOTA-TLX591,
      given notionally 14 days apart, plus best SoC.

      Twenty-five patients will also be enrolled in a biodistribution and dosimetry sub-study,
      involving the collection of quantitative single-photon emission computerized tomography
      (SPECT) or single-photon emission computerized tomography/computerized tomography (SPECT/CT)
      data in a subset of patients.

      SPECT/CT scans will be performed after administration of the drug, at the following
      timepoints: i) 4h ± 5 min, ii) 24 ± 4h, iii) 96 ± 4h, iv) Day 7± 4h and v) Day 13± 4h. These
      SPECT/CT scans will be conducted to further support safety monitoring and to understand
      exposure of tumour and healthy tissue to 177Lu-DOTA-TLX591.

      Imaging data from the first five patients enrolled in the biodistribution study will be
      analysed and, if appropriate, the number of imaging timepoints will be reduced to three for
      subsequent patients. Qualitative comparison of 68Ga-PSMA-PET/CT images and 177Lu-DOTA-TLX591
      images will also be undertaken for patients undergoing the biodistribution study to ensure
      equivalence of radiopharmaceutical localization to tumour sites and equivalent off-target
      localization.

      Blood samples for pharmacokinetic analysis will be performed at 15 min ± 5 min before
      administration of the drug, and at the following timepoints after dosing: i) end of infusion
      ± 5min, ii) 60 min ± 5 min, ii) 4h ± 5 min, iii) 24 ± 4h, v) 48 ± 4h, vi) 96 ± 4h, vii) Day
      7± 4h and viii) Day 13± 4h.

      Collection of information on prior and concomitant medications and adverse events (AEs), as
      well as the review of temporary contra-indications and conditions for withdrawal, will occur
      at every patient interaction.
    

Intervention name(s): 177Lu-DOTA-TLX591
Intervention type(s): Biological
Intervention description(s): TLX591, a monoclonal antibody HuX591 conjugated with a DOTA chelator and radiolabelled with 177Lu (177Lu-TLX591)
Intervention model: Single Group Assignment
Intervention model description: Approximately 50 eligible patients will be enrolled and evaluated for safety and tolerability as well as undergo imaging to allow determination of the biodistribution and dosimetry 177Lu-DOTA-TLX591. Twenty-five patients will also be enrolled in a biodistribution and dosimetry sub-study, involving the collection of quantitative single-photon emission computerized tomography (SPECT) or single-photon emission computerized tomography/computerized tomography (SPECT/CT) data in a subset of patients.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: prostate cancer; biodistribution; 177Lu-DOTA-TLX591; pharmacokinetics; dosimetery; safety; preliminary efficacy; standard of care; gallium-68 labeled PSMA-11 (68Ga-PSMA-11) PET/CT scan; novel androgen axis drug