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

Phase 1

Recruiting

• Conditions: Metastatic Neuroendocrine Prostate Cancer
• Interventions: Drug: [68Ga]Ga-PSMA-11; Drug: [68Ga]GA-DOTA-TATE; Drug: [68Ga]Ga-NeoB; Drug: [177Lu]Lu-PSMA-617; Drug: [177Lu]Lu-DOTA-TATE; Drug: [177Lu]Lu-NeoB; Drug: Gonadotropin-releasing hormone (GnRH) analogues; Drug: L-Lysine HCl-L-Arginine HCl, 2.5 %,; Drug: GnRH antagonists; Drug: Antiemetics & antinauseants; Drug: Metoclopramide

• Registration Number: NCT06379217
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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 Gastrin Releasing Peptide 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).

Detailed Description

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.

Study Timeline

• Study First Submitted: 2024-03-04
• Study First Submitted QC: 2024-04-17
• Study First Posted: 2024-04-23
• Study Start: 2024-07-29
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-03
• Last Update Posted: 2025-04-04
• Primary Completion: 2027-06-22
• Study Completion: 2027-06-22

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 36

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PSMA-predominant NEPC	[68Ga]Ga-PSMA-11	-
PSMA-predominant NEPC	[68Ga]GA-DOTA-TATE	-
PSMA-predominant NEPC	[68Ga]Ga-NeoB	-
PSMA-predominant NEPC	[177Lu]Lu-PSMA-617	-
PSMA-predominant NEPC	Gonadotropin-releasing hormone (GnRH) analogues	-
SSTR2-predominant NEPC	[68Ga]Ga-PSMA-11	-
SSTR2-predominant NEPC	[68Ga]GA-DOTA-TATE	-
SSTR2-predominant NEPC	[68Ga]Ga-NeoB	-
SSTR2-predominant NEPC	[177Lu]Lu-DOTA-TATE	-
SSTR2-predominant NEPC	Gonadotropin-releasing hormone (GnRH) analogues	-
SSTR2-predominant NEPC	Antiemetics & antinauseants	-
SSTR2-predominant NEPC	Metoclopramide	-
GRPR-predominant NEPC	[68Ga]Ga-PSMA-11	-
GRPR-predominant NEPC	[68Ga]Ga-NeoB	-
GRPR-predominant NEPC	[177Lu]Lu-NeoB	-
GRPR-predominant NEPC	Gonadotropin-releasing hormone (GnRH) analogues	-
GRPR-predominant NEPC	GnRH antagonists	-
SSTR2-predominant NEPC	L-Lysine HCl-L-Arginine HCl, 2.5 %,	-
PSMA-predominant NEPC	GnRH antagonists	-
SSTR2-predominant NEPC	GnRH antagonists	-
GRPR-predominant NEPC	[68Ga]GA-DOTA-TATE	-

Primary Outcome Measures

Name	Time	Method
Number/extent of lesions with at least a moderate uptake of any of the Radioligand Imaging (RLI)	Baseline (baseline imaging is performed during the 42 day screening period)	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 quantitative PET parameters.	End of Treatment (from date of baseline imaging scans to end of treatment scans, 7 weeks after last radioligand therapy infusion, approximately 36 weeks)	Percentage changes in quantitative 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.

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	From date of assignment to one of the treatment arms until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 31 months	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)	From date of assignment to one of the treatment arms until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 31 months	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)	From first documented evidence of CR or PR (the response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to approximately 31 months	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)	From date of assignment to one of the treatment arms until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 31 months	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.
Proportion of participants with a decline in PSA level	Baseline, Cycle 1 Day 1 (each cycle is 42 days), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, End Of Treatment, 6 weeks after End of Treatment	The PSA analysis will investigate the proportion of participants with a decline in PSA level from baseline to each visit.
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) for Radioligand Therapy (RLT)	Up to 42 days after last dose administration (Safety Follow-up) and every 12 weeks until end of long term follow up (Long-term FU) for selected AEs and SAEs	The distribution of adverse events for Radioligand Therapy (RLT) will be done via the analysis of frequencies for Adverse Events (AEs) and Serious Adverse Events (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 for [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB	Up to 42 days after last dose administration (Safety Follow-up)	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.
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) for Radioligand Imaging (RLI)	Continuously from informed consent for the first 6 weeks and selected AEs and SAEs thereafter	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.
Blood radioactivity concentration of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE, [177Lu]Lu-NeoB)	Cycle 1 Day 1 (each cycle is 42 days) pre-dose, post-dose/end of infusion (EOI) and then 0.5 hrs, 2 hrs, 4 hrs, 6 hrs 24 hrs, 48 hrs, 168 hrs post EOI. Cycle 3 Day 1 EOI, 1 hr, 48 hrs post EOI. Cycle 5 Day 1 EOI, and then 1 hr, 48 hrs post EOI.	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.
Blood mass concentration of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE, [177Lu]Lu-NeoB)	Cycle 1 Day 1 (each cycle is 42 days) pre-dose, post-dose/end of infusion (EOI) and then 0.5 hrs, 2 hr, 4 hr, 6 hrs, 24 hrs, 48 hrs 168 hrs post EOI. Cycle 3 Day 1 EOI, 1 hr, 48 hrs post EOI. Cycle 5 Day 1 EOI, and then 1 hr, 48 hrs post EOI.	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.
Observed maximum blood concentrations (Cmax) of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB	Cycle 1 Day 1 (each cycle is 42 days) pre-dose, post-dose/end of infusion (EOI) and then 0.5 hrs , 2 hrs, 4 hrs, 6 hrs, 24 hrs, 48 hrs, 168 hrs post EOI. Cycle 3 Day 1 EOI, 1 hr, 48 hrs post EOI. Cycle 5 Day 1 EOI, and then 1 hr, 48 hrs post EOI.	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
Time of maximum blood concentration (Tmax) occurence of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB	Cycle 1 Day 1 (each cycle is 42 days) pre-dose, post-dose/end of infusion (EOI) and then 0.5 hours (h), 2 hrs, 4 hrs, 6 hrs, 24 hrs, 48 hrs, 168 hrs post EOI. Cycle 3 Day 1 EOI, 1 hr, 48 hrs post EOI. Cycle 5 Day 1 EOI, and then 1 hr, 48 hrs post EOI.	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.
Area under the blood concentration time curve (AUC) of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB	Cycle 1 Day 1 (each cycle is 42 days) pre-dose, post-dose/end of infusion (EOI) and then 0.5 hrs , 2 hrs, 4 hrs, 6 hrs, 24 hrs, 48 hrs, 168 hrs post EOI. Cycle 3 Day 1 EOI, 1 hr, 48 hrs post EOI. Cycle 5 Day 1 EOI, and then 1 hr, 48 hrs post EOI.	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC will be listed and summarized using descriptive statistics.
Total systemic clerance (CL) of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB	Cycle 1 Day 1 (each cycle is 42 days) pre-dose, post-dose/end of infusion (EOI) and then 0.5 hrs, 2 hrs, 4 hrs, 6 hrs, 24 hrs, 48 hrs, 168 hrs post EOI. Cycle 3 Day 1 EOI, 1 hr, 48 hrs post EOI. Cycle 5 Day 1 EOI, and then 1 hr, 48 hrs post EOI.	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.
Volume of distribution during the terminal phase (Vz) of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB	Cycle 1 Day 1 (each cycle is 42 days) pre-dose, post-dose/end of infusion (EOI) and then 0.5 hrs, 2 hrs, 4 hrs, 6 hrs, 24 hrs, 48 hrs, 168 hrs post EOI. Cycle 3 Day 1 EOI, 1 hr, 48 hrs post EOI. Cycle 5 Day 1 EOI, and then 1 hr, 48 hrs post EOI.	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics.
Terminal half-life (T^1/2) of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB	Cycle 1 Day 1 (each cycle is 42 days) pre-dose, post-dose/end of infusion (EOI) and then 0.5 hrs, 2 hrs, 4 hrs, 6 hrs, 24 hrs, 48 hrs, 168 hrs post EOI. Cycle 3 Day 1 EOI, 1 hr, 48 hrs post EOI. Cycle 5 Day 1 EOI, and then 1 hr, 48 hrs post EOI.	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. The half-life will be listed and summarized using descriptive statistics.
Absorbed radiation doses of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB	Cycle 1 Day 1 (each cycle is 42 days), Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 8, Cycle 3 Day 1, Cycle 3 Day 3, Cycle 5 Day 1, Cycle 5 Day 3 (Cycle 3 Day 2, Cycle 3 Day 8, Cycle 5 Day 2 and Cycle 5 Day 8 where required by local authorities)	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).
Time Activity Curves (TACs) of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB	Cycle 1 Day 1 (each cycle is 42 days), Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 8, Cycle 3 Day 1, Cycle 3 Day 3, Cycle 5 Day 1, Cycle 5 Day 3 (Cycle 3 Day 2, Cycle 3 Day 8, Cycle 5 Day 2 and Cycle 5 Day 8 where required by local authorities)	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).

Trial Locations

Locations (4)

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

Nebraska Cancer Specialists; 🇺🇸 Omaha, Nebraska, United States

Memorial Sloan Kettering Cancer Ctr; 🇺🇸 New York, New York, United States

Novartis Investigative Site; 🇬🇧 Sutton, Surrey, United Kingdom