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| ID | Type | Description | Link |
|---|---|---|---|
| 2023-505655-43 | Registry Identifier | EU CTIS |
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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).
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 Safety follow-up visit.
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.
Protocol Amendment 7 follows the Sponsor's business decision to halt enrollment on 05-Jan-2026. The premature closure of the trial was not driven by any safety concerns identified in the study to date.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PSMA-predominant Neuroendocrine prostate cancer (NEPC) | Experimental |
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| Somatostatin Receptor 2 (SSTR2)-predominant NEPC | Experimental |
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| Gastrin Releasing Peptide Receptor (GRPR)-predominant NEPC | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate (ORR) | 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. | 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 |
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Key Inclusion criteria:
Participants must have metastatic prostate cancer with neuroendocrine differentiation as determined by at least one of the following:
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
Key Exclusion criteria:
Other protocol-defined inclusion/exclusion criteria may apply.
Participants must have metastatic prostate cancer
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nebraska Cancer Specialists | Omaha | Nebraska | 68130 | United States | ||
| Memorial Sloan Kettering Cancer Ctr |
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Participants will be assigned to a treatment arm based on their predominantly expressed target per PET images (based on central read):
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.
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| [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) |
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| [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). |
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| [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. |
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| [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. |
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| [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 |
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| L-Lysine HCl-L-Arginine HCl, 2.5 %, | Drug | sterile solution for infusion Lysine HCl-Arginine HCl, 2.5 % (1L) |
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| Gonadotropin-releasing hormone (GnRH) analogues | Drug | Anatomical Therapeutic Chemical [ATC] code L02AE |
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| GnRH antagonists | Drug | abarelix, degarelix, or relugolix |
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| Antiemetics & antinauseants | Drug | ATC code A04A |
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| Metoclopramide | Drug | ATC code A03FA01 |
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| Disease Control Rate (DCR) | 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. | 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) | 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. | 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) | 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. | 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 | The PSA analysis will investigate the proportion of participants with a decline in PSA level from baseline to each visit. | 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 |
| Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) for Radioligand Therapy (RLT) | 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. | 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 |
| Dose modifications for [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB | 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. | Up to 42 days after last dose administration (Safety Follow-up) |
| Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) for Radioligand Imaging (RLI) | 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. | Continuously from informed consent for the first 6 weeks and selected AEs and SAEs thereafter |
| Blood radioactivity concentration of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE, [177Lu]Lu-NeoB) | 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. | 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. |
| Blood mass concentration of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE, [177Lu]Lu-NeoB) | 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. | 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. |
| Observed maximum blood concentrations (Cmax) of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB | Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics. | 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. |
| Time of maximum blood concentration (Tmax) occurence of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB | Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics. | 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. |
| Area under the blood concentration time curve (AUC) of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB | Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC will be listed and summarized using descriptive statistics. | 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. |
| Total systemic clerance (CL) of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB | Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics. | 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. |
| Volume of distribution during the terminal phase (Vz) of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB | Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics. | 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. |
| Terminal half-life (T^1/2) of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB | Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. The half-life will be listed and summarized using descriptive statistics. | 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. |
| Absorbed radiation doses of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB | 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). | 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) |
| Time Activity Curves (TACs) of [177Lu]Lu-PSMA-617, [177Lu]Lu-DOTA-TATE and [177Lu]Lu-NeoB | 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). | 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) |
| New York |
| New York |
| 10017 |
| United States |
| Novartis Investigative Site | Nantes | 44093 | France |
| Novartis Investigative Site | München | 80377 | Germany |
| Novartis Investigative Site | Rostock | 18057 | Germany |
| Novartis Investigative Site | L'Hospitalet de Llobregat | Barcelona | 08907 | Spain |
| Novartis Investigative Site | Madrid | 28041 | Spain |
| Novartis Investigative Site | Sutton | Surrey | SM2 5PT | United Kingdom |
| Novartis Investigative Site | London | NW3 2QG | United Kingdom |
| ID | Term |
|---|---|
| C000718244 | gallium 68 PSMA-11 |
| C513399 | gallium Ga 68 dotatate |
| D005708 | Gallium |
| D008187 | Lutetium |
| C000615061 | Lutetium-177 |
| C000718307 | copper dotatate CU-64 |
| D007987 | Gonadotropin-Releasing Hormone |
| D000932 | Antiemetics |
| D008787 | Metoclopramide |
| ID | Term |
|---|---|
| D019216 | Metals, Heavy |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D008670 | Metals |
| D028581 | Lanthanoid Series Elements |
| D008674 | Metals, Rare Earth |
| D028561 | Transition Elements |
| D010906 | Pituitary Hormone-Releasing Hormones |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
| D001337 | Autonomic Agents |
| D018373 | Peripheral Nervous System Agents |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D002491 | Central Nervous System Agents |
| D045506 | Therapeutic Uses |
| D005765 | Gastrointestinal Agents |
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D062366 | para-Aminobenzoates |
| D062365 | Aminobenzoates |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D002723 | Chlorobenzoates |
| D062425 | Hydroxybenzoate Ethers |
| D062385 | Hydroxybenzoates |
| D006880 | Hydroxy Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010647 | Phenyl Ethers |
| D010636 | Phenols |
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