NCT06379217

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.

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 31 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: Male
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

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 baseline and following targeted 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). Study is planning to enroll approximately 20 participants in \[177Lu\]Lu-PSMA-617 treatment arm, approximately 3 participants in \[177Lu\]Lu-NeoB treatment arm, and approximately 13 participants in \[177Lu\]Lu-DOTA-TATE treatment arm.

Detailed description

The screening period for each participant 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 least six weeks after receiving the first cycle of RLT, participants must be scanned again with up to 3 RLIs but must be scanned, with at least with one RLI corresponding to the received RLT, which is recommended to be performed first. All post-baseline PET/CT scans should be performed using the same PET/CT imaging agent and 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, efficacy, and survival 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 ±7 days. 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.

Conditions

• Metastatic Neuroendocrine Prostate Cancer

Interventions

Type	Name	Description
DRUG	[68Ga]Ga-PSMA-11	\[68Ga\]Ga-PSMA-11 will be administered as a single intravenous dose of approximately 150 MBq (4 mCi) to be administered during baseline imaging and at any time ≥ 6 weeks after first RLT dose. Sites should consider doing PET/CT imaging with RLT corresponding RLI as the first of three PET/CT scans. Administered dose should not be lower than 111 MBq (3 mCi) or higher than 259 MBq (7 mCi)
DRUG	[68Ga]GA-DOTA-TATE	\[68Ga\]Ga-DOTA-TATE will be administered as a single intravenous dose to be administered during baseline imaging and at any time ≥ 6 weeks after first RLT dose. Sites should consider doing PET/CT imaging with RLT corresponding RLI as the first of three PET/CT scans. within a range of 100-200MBq (2.7-5.4 mCi)
DRUG	[68Ga]Ga-NeoB	\[68Ga\]Ga-NeoB will be administered as a single intravenous dose to be administered during baseline imaging and at any time ≥ 6 weeks after first RLT dose. Sites should consider doing PET/CT imaging with RLT corresponding RLI as the first of three PET/CT scans. within a range of 150-250 MBq (4.1-6.8 mCi).
DRUG	[177Lu]Lu-PSMA-617	\[177Lu\]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.
DRUG	[177Lu]Lu-DOTA-TATE	\[177Lu\]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.
DRUG	[177Lu]Lu-NeoB	\[177Lu\]Lu-NeoB will be administered as an intravenous infusion at a dose of 9.25 GBq (250mCi) every 6 weeks for 6 cycles
DRUG	L-Lysine HCl-L-Arginine HCl, 2.5 %,	sterile solution for infusion Lysine HCl-Arginine HCl, 2.5 % (1L)
DRUG	Gonadotropin-releasing hormone (GnRH) analogues	Anatomical Therapeutic Chemical \[ATC\] code L02AE
DRUG	GnRH antagonists	abarelix, degarelix, or relugolix
DRUG	Antiemetics & antinauseants	ATC code A04A
DRUG	Metoclopramide	ATC code A03FA01

Timeline

• Start date: 2024-07-29
• Primary completion: 2026-08-27
• Completion: 2026-08-27
• First posted: 2024-04-23
• Last updated: 2026-03-11

Locations

11 sites across 5 countries: United States, France, Germany, Spain, United Kingdom

Regulatory

• FDA-regulated drug study