Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Pharmaceutical Solutions

Antiemetics

Gastrointestinal Agents

Cardiotonic Agents

Amino Acids

Gallium 68 PSMA-11

Hormones

Somatostatin

Relugolix

Lutetium Lu 177 dotatate

Metoclopramide

Gastrins

Bombesin

Gastrin-Releasing Peptide

Abarelix

Prolactin Release-Inhibiting Factors

1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid

Hormone Antagonists

Chelating Agents

Radiopharmaceuticals

Dopamine

Dopamine Antagonists

Dopamine Agents

Neurotransmitter Agents

Arginine

Lysine

\[68Ga\]Ga-PSMA-11 will be administered as a single intravenous dose of approximately 150 MBq (4 mCi) to be administered during baseline imaging and approximately 7 weeks after last RLT dose. Administered dose should not be lower than 111 MBq (3 mCi) or higher than 259 MBq (7 mCi)

[68Ga]Ga-PSMA-11

\[68Ga\]Ga-DOTA-TATE will be administered as a single intravenous dose to be administered during baseline imaging and approximately 7 weeks after last RLT dose, within a range of 100-200MBq (2.7-5.4 mCi)

[68Ga]GA-DOTA-TATE

\[68Ga\]Ga-NeoB will be administered as a single intravenous dose to be administered during baseline imaging and approximately 7 weeks after last RLT dose.within a range of 150-250 MBq (4.1-6.8 mCi).

[68Ga]Ga-NeoB

\[177Lu\]Lu-PSMA-617 will be administered as an intravenous infusion at a dose of 7.4 GBq (200mCi) (+/- 10%), every 6 weeks for 6 cycles.

[177Lu]Lu-PSMA-617

\[177Lu\]Lu-DOTA-TATE will be administered as an intravenous infusion at a dose of 7.4 GBq (200mCi) (+/- 10%) every 6 weeks for 6 cycles.

[177Lu]Lu-DOTA-TATE

\[177Lu\]Lu-NeoB will be administered as an intravenous infusion at a dose of 9.25 GBq (250mCi) every 6 weeks for 6 cycles

[177Lu]Lu-NeoB

sterile solution for infusion Lysine HCl-Arginine HCl, 2.5 % (1L)

L-Lysine HCl-L-Arginine HCl, 2.5 %,

Anatomical Therapeutic Chemical \[ATC\] code L02AE

Gonadotropin-releasing hormone (GnRH) analogues

GnRH antagonists

Antiemetics & antinauseants

Novartis Pharmaceuticals

The purpose of this study is to evaluate the change in the expression of treatment targets on the surface of tumor cells (Prostate Specific Membrane Antigen (PSMA), Somatostatin Receptor 2 (SSTR2), and Gonadotropin Releasing Hormone Receptor (GRPR)) between the start and after the completion of radioligand therapy (RLT). Study will use radioligand imaging (RLI) to determine predominantly expressed target on the surface of tumor cells. Based on predominant expression of target, corresponding RLT targeting PSMA, SSTR2, or GRPR RLT will be given for up to 6 cycles every 6 weeks as intravenous (i.v.) injection in participants with metastatic neuroendocrine prostate cancer (mNEPC).

The screening period for each subject includes imaging with 3 radioligand imaging (RLI) compounds to assess expression level of PSMA, SSTR2 and GRPR. Participants will be assigned to the radioligand treatment (RLT) corresponding to their predominantly expressed target based on blinded independent central review (BICR). During the treatment period, participants will receive up to 6 cycles of the assigned RLT, corresponding to a total dose of 44.4 GBq (+/-10%) for \[177Lu\]Lu-PSMA-617 or \[177Lu\]Lu-DOTA-TATE , and 55.5 GBq (+/-10%) for \[177Lu\]Lu-NeoB. No crossover to a different type of RLT is allowed.

At end of treatment (EoT) with RLT, participants will be scanned again with the 3 RLIs. All EoT PET/CT scans should be performed using the same PET/CT camera, acquisition and reconstruction protocols as used for screening PET/CT for the participant.

The post-treatment follow-up period consists of a 42-days post EoT safety follow-up visit and long-term follow-up until radiographic disease progression, death, lost to follow-up or withdrawal of consent, whichever occurs first.

The planned duration of treatment is up to 36 weeks for all treatment arms in this study, with treatment given every 6 weeks. Participants may be discontinued from treatment earlier due to unacceptable toxicity or disease progression, and/or at the discretion of the Investigator or the participant.

Participants will be assigned to a treatment arm based on their predominantly expressed target per PET images (based on central read):

* \[177Lu\]Lu-PSMA-617 will be assigned to those with predominant PSMA expression
* \[177Lu\]Lu-DOTA-TATE will be assigned to those with predominant SSTR2 expression
* \[177Lu\]Lu-NeoB will be assigned to those with predominant GRPR expression

Participants must have metastatic prostate cancer

NEPC Study: An Exploratory Safety and Efficacy Study With PSMA, SSTR2 and GRPR Targeted Radioligand Therapy in Metastatic Neuroendocrine Prostate Cancer.

A Phase I, Open-label, Multi-center Exploratory Safety and Efficacy Study With PSMA, SSTR2 and GRPR Targeted Radioligand Therapy in Metastatic Neuroendocrine Prostate Cancer.

Number/extent of lesions with at least a moderate update of any of the RLIs according to visual assessment scoring scale on each corresponding targeted PET/CT scan based on blinded independent central review (BICR) assessment.

Percentage changes in qualitative PET parameters (SUVmax, SUVmean, SUVpeak, target-positive Tumor Volume (target -TV), Total Lesion (target (TL-target)\] and changes in number of target-positive lesions (as per visual assessment) on each corresponding target PET/CT based on BICR.

Overall Response Rate (ORR) is defined as the proportion of participants with the best overall response (BOR) of confirmed complete response (CR) or partial response (PR) based on Prostate Cancer Working Group 3 (PCWG3) modified-RECIST v1.1.

Disease Control Rate (DCR) is defined as the proportion of participants with BOR of CR, PR, stable disease (SD), or non-CR/non-PD based on PCWG3 modified-RECIST v1.1.

Duration of response (DOR) is defined as the time (in months) from the date of the first confirmed response (CR or PR) to the date of first documented progression according to PCWG3 modified-RECIST v1.1 or death due to any cause, among participants with a confirmed response.

Radiographic Progression-free Survival (rPFS) is defined as the time from the date of first dose of study treatment to the date of first documented radiographic progression (as assessed by the local investigator and using PCWG3 modified-RECIST v1.1 criteria) or death due to any cause.

The PSA analysis will investigate the proportion of participants with a decline in PSA level from baseline to each visit.

The distribution of adverse events for Radioligand Therapy (RLT) will be done via the analysis of frequencies for Adverse Event (AEs) and Serious Adverse Event (SAEs) through the monitoring of relevant clinical and laboratory safety parameters.

Adverse event monitoring should be continued for at least 42 days following the end of treatment (EOT) visit.

Participants receiving the study treatment \[68Ga\]Ga-DOTA-TATE/\[177Lu\]Lu-PSMA-617 or \[177Lu\]Lu-NeoB will continue to be followed for safety every 12 weeks during the long-term follow-up for selected adverse events.

Dose modifications (dose interruptions, dose discontinuations and reductions) for \[177Lu\]Lu-PSMA-617, \[177Lu\]Lu-DOTA-TATE and \[177Lu\]Lu-NeoB will be assessed and summarized using descriptive statistics.

The distribution of adverse events for Radioligand Imaging (RLI) will be done via the analysis of frequencies for Adverse Event (AEs) and Serious Adverse Event (SAEs) through the monitoring of relevant clinical and laboratory safety parameters.

Data will be listed by participant and visit/sampling time point. Descriptive summary statistics will be provided by visit/sampling time point and treatment arm including the frequency (n, %) of concentrations below the lower limit of quantification (LLOQ) and reported as zero.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. The half-life will be listed and summarized using descriptive statistics.

The analysis of biodistribution and dosimetry endpoints will consist of descriptive summaries and graphical presentations of the derived parameters. For each of the treatments, the absorbed dose by body organs and tumor lesions will be determined by calculation of TACs obtained from the radiotracer uptake (as percentage of injected dose) in selected organs and lesions (coming from image quantification).

Spots Global Cancer Trial Database for metastatic neuroendocrine prostate cancer