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

Purpose

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.

Condition

  • Metastatic Neuroendocrine Prostate Cancer

Eligibility

Eligible Ages
Between 18 Years and 100 Years
Eligible Sex
Male
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Participants must have metastatic prostate cancer with neuroendocrine differentiation as determined by at least one of the following: 1. Histologically small cell or neuroendocrine cancer from a primary prostate or metastatic biopsy confirmed by local laboratory. 2. Expression of NEPC markers (e.g., chromogranin or synaptophysin) in tumor tissue by IHC confirmed by local laboratory 3. Progression of visceral metastases in the absence of PSA progression 4. Serum chromogranin A > 5x normal limit, or neuron-specific enolase > 2x normal limit with control for proton-pump inhibitors (PPI) drugs among concomitant treatment 5. 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

Exclusion Criteria

  • 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 Other protocol-defined inclusion/exclusion criteria may apply.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
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.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
PSMA-predominant NEPC
  • 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)
    Other names:
    • Gallium (68Ga) gozetotide
  • 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)
    Other names:
    • Gallium (68Ga) DOTA-TATE
  • 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).
    Other names:
    • Gallium (68Ga) NeoB
  • 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.
    Other names:
    • Lutetium (177Lu) vipivotide tetraxetan
  • Drug: Gonadotropin-releasing hormone (GnRH) analogues
    Anatomical Therapeutic Chemical [ATC] code L02AE
  • Drug: GnRH antagonists
    abarelix, degarelix, or relugolix
Experimental
SSTR2-predominant NEPC
  • 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)
    Other names:
    • Gallium (68Ga) gozetotide
  • 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)
    Other names:
    • Gallium (68Ga) DOTA-TATE
  • 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).
    Other names:
    • Gallium (68Ga) NeoB
  • 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.
    Other names:
    • Lutetium (177Lu) DOTA-TATE
  • Drug: L-Lysine HCl-L-Arginine HCl, 2.5 %,
    sterile solution for infusion Lysine HCl-Arginine HCl, 2.5 % (1L)
    Other names:
    • Lysine HCl-Arginine HCl, 2.5 %
  • 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
Experimental
GRPR-predominant NEPC
  • 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)
    Other names:
    • Gallium (68Ga) gozetotide
  • 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)
    Other names:
    • Gallium (68Ga) DOTA-TATE
  • 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).
    Other names:
    • Gallium (68Ga) NeoB
  • 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
    Other names:
    • Lutetium (177Lu) NeoB
  • Drug: Gonadotropin-releasing hormone (GnRH) analogues
    Anatomical Therapeutic Chemical [ATC] code L02AE
  • Drug: GnRH antagonists
    abarelix, degarelix, or relugolix

Recruiting Locations

Stanford University
Palo Alto 5380748, California 5332921 94304
Contact:
Tiffany Chen
tiff1221@stanford.edu

Nebraska Cancer Specialists
Omaha 5074472, Nebraska 5073708 68130
Contact:
Jena Depue
402-691-6972
jdepue@nebraskacancer.com

Memorial Sloan Kettering Cancer Ctr
New York 5128581, New York 5128638 10017
Contact:
Andy Casillas
+1 646 422 4379
casilla@mskcc.org

Seattle Cancer Care Alliance
Seattle 5809844, Washington 5815135 98109
Contact:
Jane Romani
206-288-2056
jromani@fredhutch.org

More Details

NCT ID
NCT06379217
Status
Recruiting
Sponsor
Novartis Pharmaceuticals

Study Contact

Novartis Pharmaceuticals
1-888-669-6682
novartis.email@novartis.com

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.

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