[Lu-177]Ludotadipep in Castration-resistant Prostate Cancer(CRPC): Investigation of Drug and Application

Phase 1:

The patient will attend a Screening visit (-28 to -1 days) prior to study treatment, where it will be determined if the patient is eligible to, and consents to, participate in the trial based on the inclusion/exclusion criteria. \[Ga-68\]PSMA-11 positron emission tomography (PET)/CT scan will be performed at screening.

Patients who are finally registered for trial participation will be injected with a single dose of \[177Lu\]Ludotadipep. Ice packs and other cooling therapies will be applied to the major salivary glands from 30 minutes before the administration of \[177Lu\]Ludotadipep to 60 minutes after the administration to prevent side effects such as sialadenitis. Amino acid solution will be administered slowly intravenously for renal protection over approximately 4 hours from 30 minutes before treatment to 3.5 hours after treatment. 500 mL of 0.9% sodium chloride (NaCl) will be administered slowly intravenously for hydration over approximately 90 minutes from 30 minutes before treatment to 60 minutes after treatment.

Adverse events and DLTs will be assessed continuously for the duration of the 8 \[±1\] week study period. Other measurements, corresponding to secondary outcomes, are detailed in the Schedule of Assessments and include concomitant medications, laboratory tests, physical examination, vital signs, Eastern cooperative oncology group performance status (ECOG PS), imaging (positron emission tomography-computed tomography \[PET/CT\], bone scan and Whole Body Scan (WBS)). Follow-up will occur at scheduled visits 1, 2, 4 and 8 weeks after investigational product (IP) administration.

Patients who show a clinical response and who the PI considers will likely benefit from retreatment can be so treated after consultation and agreement of the medical monitor and the sponsor.

Phase 2a:

The patient will attend a Screening visit (-28 to -1 days) prior to treatment with IP, where it will be determined if the patient is eligible to, and consents to, participate in the trial based on the inclusion/exclusion criteria. \[Ga-68\]PSMA-11 PET/CT and \[F-18\]FDG-PET scans will be performed at screening.

Patients who are finally registered for trial participation will be injected with a single dose of \[177Lu\]Ludotadipep. Ice packs and other cooling therapies will be applied to the major salivary glands 30 minutes before and up to 60 minutes after the administration of \[177Lu\]Ludotadipep to prevent side effects such as sialadenitis. Amino acid solution will be administered slowly intravenously for renal protection over approximately 4 hours from 30 minutes before treatment to 3.5 hours after treatment. 500 mL of 0.9% NaCl will be administered slowly intravenously for hydration over approximately 90 minutes from 30 minutes before treatment to 60 minutes after treatment. WBS or single photon emission computed tomography (SPECT) images will be obtained 24 hours after each administration and Day 7, and AE information will also be captured. Other measurements are detailed in the Schedule of Assessments.