Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Pharmaceutical Solutions

Antiemetics

Gastrointestinal Agents

Cardiotonic Agents

Amino Acids

Gallium 68 PSMA-11

Hormones

Somatostatin

Relugolix

Lutetium Lu 177 dotatate

Metoclopramide

Gastrins

Bombesin

Gastrin-Releasing Peptide

Abarelix

Prolactin Release-Inhibiting Factors

1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid

Hormone Antagonists

Chelating Agents

Radiopharmaceuticals

Dopamine

Dopamine Antagonists

Dopamine Agents

Neurotransmitter Agents

Arginine

Lysine

\[68Ga\]Ga-PSMA-11 will be administered as a single intravenous dose of approximately 150 MBq (4 mCi) to be administered during baseline imaging and approximately 7 weeks after last RLT dose. Administered dose should not be lower than 111 MBq (3 mCi) or higher than 259 MBq (7 mCi)

[68Ga]Ga-PSMA-11

\[68Ga\]Ga-DOTA-TATE will be administered as a single intravenous dose to be administered during baseline imaging and approximately 7 weeks after last RLT dose, within a range of 100-200MBq (2.7-5.4 mCi)

[68Ga]GA-DOTA-TATE

\[68Ga\]Ga-NeoB will be administered as a single intravenous dose to be administered during baseline imaging and approximately 7 weeks after last RLT dose.within a range of 150-250 MBq (4.1-6.8 mCi).

[68Ga]Ga-NeoB

\[177Lu\]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.

[177Lu]Lu-PSMA-617

\[177Lu\]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.

[177Lu]Lu-DOTA-TATE

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

[177Lu]Lu-NeoB

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

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

Anatomical Therapeutic Chemical \[ATC\] code L02AE

Gonadotropin-releasing hormone (GnRH) analogues

GnRH antagonists

Antiemetics & antinauseants

Novartis Pharmaceuticals

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 Gonadotropin Releasing Hormone 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).

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.

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

Participants must have metastatic prostate cancer

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.

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 qualitative 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.

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) 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) 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) 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.

The PSA analysis will investigate the proportion of participants with a decline in PSA level from baseline to each visit.

The distribution of adverse events for Radioligand Therapy (RLT) 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.

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 (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.

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.

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.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. The half-life will be listed and summarized using descriptive statistics.

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).

Respiratory Tract (Lung and Bronchial) Diseases

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

Micronutrients

Hematinics

Vitamins

Folic Acid

Vitamin B Complex

Folinic Acid

Folate

Vitamin B9

Patients will receive \[68Ga\]Ga-EVS459 and, if eligible, \[177Lu\]Lu-EVS459

[68Ga]Ga-EVS459

[177Lu]Lu-EVS459

The purpose of this study is to evaluate the safety, tolerability, dosimetry and preliminary efficacy of \[177Lu\]Lu-EVS459 and the safety and imaging properties of \[68Ga\]Ga-EVS459 in patients aged ≥ 18 years with advanced high-grade serous ovarian cancer (OC) or locally advanced unresectable or metastatic non-squamous non-small cell lung carcinoma (non-sq. NSCLC).

The study will be done in two parts. The first part is called "escalation" and the second part is called "expansion". In both parts of the study, patients will initially be imaged with a \[68Ga\]Ga EVS459 positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance imaging (MRI) scan. In the escalation part, different doses of \[177Lu\]Lu-EVS459 will then be tested to identify recommended dose(s) (RD(s)) for further evaluation. The expansion part of the study will examine the safety and preliminary efficacy of \[177Lu\]Lu-EVS459 at the RD(s) determined during the escalation part. The end of study will occur when at least 80% of the patients in the expansion part have completed the follow-up for disease progression or discontinued from the study for any reason, and all patients have completed treatment and the 36-month long-term follow-up period.

A Phase I Study of [177Lu]Lu-EVS459 in Patients With Ovarian and Lung Cancers

A Phase I, Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry, and Preliminary Activity of [177Lu]Lu-EVS459 in Patients With Ovarian and Lung Cancers

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

A dose limiting toxicity (DLT) is defined as any adverse event or abnormal laboratory value of CTCAE (version 5.0) Grade 3 or higher that occurs within the DLT evaluation period and that is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications with a few exceptions defined in the study protocol. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.

The distribution of adverse events will be done via the analysis of frequencies for treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) and through the monitoring of relevant clinical and laboratory safety parameters.

Dose modifications (dose interruptions and reductions) for \[177Lu\]Lu-EVS459 will be assessed and summarized using descriptive statistics. The number of patients with dose modification will be summarized by treatment groups.

Dose intensity for \[177Lu\]Lu- EVS459 will be assessed and summarized using descriptive statistics. Dose intensity is computed as the ratio of actual cumulative dose received and actual duration of exposure.

ORR is defined as the proportion of patients with a BOR of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines.

DOR is the time between the first documented response (CR or PR) and the date of progression according to RECIST v1.1 guidelines.

DCR is defined as the proportion of patients with a BOR of CR, PR, or stable disease according to RECIST v1.1 guidelines.

PFS is defined as the time from the date of start of treatment to the date of the first documented progression according to RECIST v1.1 guidelines or death due to any cause.

The \[177Lu\]Lu-EVS459 pharmacokinetic analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. AUC will be determined by non-compartmental methods.

The \[177Lu\]Lu-EVS459 pharmacokinetic analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. Total body clearance will be determined by non-compartmental methods.

The \[177Lu\]Lu-EVS459 pharmacokinetic analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. Cmax will be determined by non-compartmental methods.

The \[177Lu\]Lu-EVS459 pharmacokinetic analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. Vz will be determined by non-compartmental methods.

The \[177Lu\]Lu-EVS459 pharmacokinetic analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. T1/2 will be determined by non-compartmental methods.

Urine elimination data for \[177Lu\]Lu-EVS459 will be assessed based on decay-corrected urine radioactivity concentration data. Urine elimination data will be expressed as percentage of injected activity (%IA).

Urine samples will be collected over specified time intervals and analysed for radioactivity. Renal clearance of 177Lu-EVS459 will be summarized using descriptive statistics.

The absorbed dose in normal tissues and tumor lesions will be summarized with descriptive statistics.

Lesion number will be assigned by dosimetry expert.

Time-activity curves (TACs) for the various organs and tumor lesions will be produced as fraction of injected activity per gram of tissue (%IA/g) as a function of time.

After \[68Ga\]Ga-EVS459 administration, \[68Ga\]Ga-EVS459 PET/CT or PET/MRI will be performed. Standardized uptake values (SUVs) of \[68Ga\]Ga-EVS459 in normal tissues and tumor lesions over time will be summarized.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
NEPC Study: An Exploratory Safety and Efficacy Study With PSMA, SSTR2 and GRPR Targeted Radioligand Therapy in Metastatic Neuroendocrine Prostate Cancer.	NCT06379217	Metastatic Neur...	[68Ga]Ga-PSMA-1... [68Ga]GA-DOTA-T... [68Ga]Ga-NeoB [177Lu]Lu-PSMA-... [177Lu]Lu-DOTA-... [177Lu]Lu-NeoB L-Lysine HCl-L-... Gonadotropin-re... GnRH antagonist... Antiemetics & a... Metoclopramide	18 Years -	Novartis
A Phase I Study of [177Lu]Lu-EVS459 in Patients With Ovarian and Lung Cancers	NCT06376253	Ovarian Cancer Lung Cancer	[68Ga]Ga-EVS459 [177Lu]Lu-EVS45...	18 Years - 100 Years	Novartis

Spots Global Cancer Trial Database for radioligand therapy (rlt)