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

NCT06379217 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: CAAA617H121012023-505655-43
• Study Type: interventional
• Target: 31
• Locations: 5 countries
• Sites: 11

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 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.

Conditions

Metastatic Neuroendocrine Prostate Cancer

Keywords

[68Ga]Ga-PSMA-11; [177Lu]Lu-PSMA-617; [68Ga]Ga-DOTA-TATE; [177Lu]Lu-DOTA-TATE; [68Ga]Ga-NeoB; [177Lu]Lu-NeoB; Neuroendocrine prostate cancer (NEPC); Metastatic Neuroendocrine Prostate Cancer (mNEPC); Radioligand Imaging (RLI); Radioligand Therapy (RLT); Prostate-specific membrane antigen (PSMA); Somatostatin Receptor 2 (SSTR2); Gastrin Releasing Peptide Receptor (GRPR); Phase 1

Outcome Measures

Primary Outcomes (2)

• Number/extent of lesions with at least a moderate uptake of any of the Radioligand Imaging (RLI)

  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.

  Baseline (baseline imaging is performed during the 42 day screening period)

• Percentage changes in quantitative PET parameters.

  Percentage changes in quantitative PET/CT 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.

  Post-Baseline (from date of baseline imaging scans to post-baseline scans, at least 6 weeks after receiving the first cycle of radioligand treatment)

Secondary Outcomes (18)

• 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

• 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

• 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

• 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

• 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

Study Arms (3)

PSMA-predominant NEPC

EXPERIMENTAL

Drug: [68Ga]Ga-PSMA-11; Drug: [68Ga]GA-DOTA-TATE; Drug: [68Ga]Ga-NeoB; Drug: [177Lu]Lu-PSMA-617; Drug: Gonadotropin-releasing hormone (GnRH) analogues; Drug: GnRH antagonists

SSTR2-predominant NEPC

EXPERIMENTAL

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

GRPR-predominant NEPC

EXPERIMENTAL

Drug: [68Ga]Ga-PSMA-11; Drug: [68Ga]GA-DOTA-TATE; Drug: [68Ga]Ga-NeoB; Drug: [177Lu]Lu-NeoB; Drug: Gonadotropin-releasing hormone (GnRH) analogues; Drug: GnRH antagonists

Interventions

[68Ga]Ga-PSMA-11 DRUG

\[68Ga\]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)

Also known as: Gallium (68Ga) gozetotide

GRPR-predominant NEPC; PSMA-predominant NEPC; SSTR2-predominant NEPC

[68Ga]GA-DOTA-TATE DRUG

\[68Ga\]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)

Also known as: Gallium (68Ga) DOTA-TATE

GRPR-predominant NEPC; PSMA-predominant NEPC; SSTR2-predominant NEPC

[68Ga]Ga-NeoB DRUG

\[68Ga\]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).

Also known as: Gallium (68Ga) NeoB

GRPR-predominant NEPC; PSMA-predominant NEPC; SSTR2-predominant NEPC

[177Lu]Lu-PSMA-617 DRUG

\[177Lu\]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.

Also known as: Lutetium (177Lu) vipivotide tetraxetan

PSMA-predominant NEPC

[177Lu]Lu-DOTA-TATE DRUG

\[177Lu\]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.

Also known as: Lutetium (177Lu) DOTA-TATE

SSTR2-predominant NEPC

[177Lu]Lu-NeoB DRUG

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

Also known as: Lutetium (177Lu) NeoB

GRPR-predominant NEPC

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

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

Also known as: Lysine HCl-Arginine HCl, 2.5 %

SSTR2-predominant NEPC

Gonadotropin-releasing hormone (GnRH) analogues DRUG

Anatomical Therapeutic Chemical \[ATC\] code L02AE

GRPR-predominant NEPC; PSMA-predominant NEPC; SSTR2-predominant NEPC

GnRH antagonists DRUG

abarelix, degarelix, or relugolix

GRPR-predominant NEPC; PSMA-predominant NEPC; SSTR2-predominant NEPC

Antiemetics & antinauseants DRUG

ATC code A04A

SSTR2-predominant NEPC

Metoclopramide DRUG

ATC code A03FA01

SSTR2-predominant NEPC

Eligibility Criteria

• Age: 18 Years - 100 Years
• Gender Eligibility Details: Participants must have metastatic prostate cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have metastatic prostate cancer with neuroendocrine differentiation as determined by at least one of the following:
• Histologically small cell or neuroendocrine cancer from a primary prostate or metastatic biopsy confirmed by local laboratory.
• Expression of NEPC markers (e.g., chromogranin or synaptophysin) in tumor tissue by IHC confirmed by local laboratory
• Progression of visceral metastases in the absence of PSA progression
• Serum chromogranin A \> 5x normal limit, or neuron-specific enolase \> 2x normal limit with control for proton-pump inhibitors (PPI) drugs among concomitant treatment
• Prostate adenocarcinoma with molecular features of neuroendocrine differentiated cancer (e.g., 2 of the following 3: PTEN, TP53, or RB loss)
• PSMA and/or SSTR2 and/or GRPR PET-positive participants, with at least one measurable lesion per RECIST 1.1 with moderate target expression in at least one of the 3 PET/CT scans per BICR assessment
• Castrate level of serum/plasma testosterone (\< 50 ng/dl, or \< 1.7 nmol/L) for participants with adenocarcinoma component or stable testosterone level for participants with pure neuroendocrine carcinoma
• Recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapy
• Participant has adequate bone marrow and organ function (as assessed by central laboratory for eligibility)
• ECOG status =\< 2

You may not qualify if:

• Previous treatment with any of the following within 6 months prior to Screening: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation
• Previous PSMA, SSTR2, or GRPR targeted radioligand therapy
• Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy or investigational therapy
• History of CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity
• Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
• History or current diagnosis of ECG abnormalities indicating significant risk of safety for study participants

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (11)

Stanford University

Palo Alto, California, 94304, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

Memorial Sloan Kettering Cancer Ctr

New York, New York, 10017, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Novartis Investigative Site

Nantes, 44093, France

Location

Novartis Investigative Site

München, 80377, Germany

Location

Novartis Investigative Site

Rostock, 18057, Germany

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Novartis Investigative Site

London, NW3 2QG, United Kingdom

Location

MeSH Terms

Interventions

gallium 68 PSMA-11; gallium Ga 68 dotatate; Gallium; Lutetium; Lutetium-177; copper dotatate CU-64; Gonadotropin-Releasing Hormone; Antiemetics; Metoclopramide

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Metals; Lanthanoid Series Elements; Metals, Rare Earth; Transition Elements; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Central Nervous System Agents; Therapeutic Uses; Gastrointestinal Agents; Benzamides; Amides; Organic Chemicals; para-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Chlorobenzoates; Hydroxybenzoate Ethers; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenyl Ethers; Phenols

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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 In complex cases the local Investigator has the authority to make decisions on the most appropriate RLT assignment. If the selected RLT assignment is to a treatment arm that has reached its maximum enrollment, the patient will not be able to receive the selected RLT and will not join the treatment phase.

Study Record Dates

• First Submitted: March 4, 2024
• First Posted: April 23, 2024
• Study Start: July 29, 2024
• Primary Completion (Estimated): August 27, 2026
• Study Completion (Estimated): August 27, 2026
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); FR (1); DE (2); US (4); ES (2)