68Ga-OPS202 Study for Diagnostic Imaging of GEP NET

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of 68Ga-OPS202 used for the diagnosis of gastroenteropancreatic neuroendocrine tumors (GEP NETs).

Official Title
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An Open-label, Micro-dosing Study to Evaluate Safety, Biodistribution, Dosimetry and Preliminary Efficacy of Two Single 68Ga-OPS202 Doses for the Diagnostic Imaging of Somatostatin Receptor-positive Gastro-entero-pancreatic Neuroendocrine Tumors (GEP NET) Using Positron-emission Tomography / Computed Tomography (PET/CT)

Conditions
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Gastroenteropancreatic Neuroendocrine Tumors

Intervention / Treatment
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* Drug: satoreotide trizoxetan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diagnostic CT or MRI of the tumor region within the previous 6 months prior to dosing day is available. A somatostatin receptor scan with results in the previous 6 months prior to dosing day. At least 1 lesion detected by the previous somatostatin receptor scan. Not exceeding 30 lesions / organ detected by the previous somatostatin receptor scan. Blood test results as follows (WBC: ≥ 3*109/L, Hemoglobin: ≥ 8.0 g/dL, Platelets: ≥ 50x109/L, ALT, AST, AP: ≤ 5 times ULN, Bilirubin: ≤ 3 times ULN) ECG: any abnormalities have to be clarified by a cardiologist. Serum creatinine: within normal limits or < 120 μmol/L for patients aged 60 years or older. Calculated GFR ≥ 45 mL/min. Negative pregnancy test in women capable of child-bearing. Exclusion Criteria: Known hypersensitivity to 68Ga, to NODAGA, to JR11 or to any of the excipients of 68Ga-OPS202. History of, or current active allergic or autoimmune disease, including asthma or any condition requiring long-term use of corticosteroids. Presence of active infection at screening or history of serious infection within the previous 6 weeks. Known human immunodeficiency virus (HIV) or positive serology for HIV, hepatitis B and C. Any condition that precludes raised arms position for prolonged imaging purposes. Neuroendocrine tumor specific treatment between last somatostatin receptor imaging and start of this study. Exception is the therapeutic use of any somatostatin analog (see below). Therapeutic use of any somatostatin analog, including Sandostatin® LAR (within 28 days) and Sandostatin® (within 2 days) prior to study imaging. If a patient is on Sandostatin® LAR a wash-out phase of 28 days is required before the injection of the study drug. If a patient is on Sandostatin® a wash-out phase of 2 days is required before the injection of the study drug. Administration of another investigational medicinal product within 30 days prior to entry. Prior or planned administration of a radiopharmaceutical within 8 half-lives of the radionuclide used on such radiopharmaceutical including at any time during the current study. Current > grade 2 toxicity from previous standard or investigational therapies, per US-NCI Common Terminology Criteria for Adverse Events v4.0. Pregnant or breast-feeding women. History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study. Clinically significant illness or clinically relevant trauma within 2 weeks before the administration of the investigational product. Current history of malignancy; patients with a secondary tumor in remission of > 5 years can be included.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 68Ga-OPS202<br>Satoreotide trizoxetan will be administered in two sequentially ascending peptide doses | Drug: satoreotide trizoxetan<br> <br> * Other names: 68Ga-OPS202;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reported With Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Drug Reactions (ADRs) | An AE was defined as any untoward medical occurrence in a participant administered a IP and which does not necessarily have a causal relationship with this treatment. For this study, all AEs were regarded as 'treatment emergent', i.e., not seen before administration of the IP or, if already present before administration, worsened after start of administration. An SAE was defined as an event that led to death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect. An ADR was defined as an AE with probable, possible or unlikely relationship to the administration of 68Ga-OPS202. | From start of IP administration to end of the study visit (approximately 28 to 36 days) | 
| Number of Participants With Clinical Significant Abnormalities in Laboratory Parameters, Vital Signs, Cardiac Safety, Physical Examination, and Required Concomitant Medication | Laboratory assessments included hematology, blood biochemistry and urine analysis. Vital signs included systolic and diastolic blood pressure, heart rate and axillary body temperature. Cardiac safety was assessed by 12-lead ECGs and physical examination included general appearance, head, neck, eyes, ears, nose, throat, respiratory, cardiovascular, gastrointestinal, musculoskeletal, neurological, endocrine, lymphatic, dermatological, psychological/psychiatric, abdomen, and genitourinary body systems. All medications (including herbal products) taken from visit 1 (Day 0) to visit 3 (7-15 days after visit 2 (3-4 weeks after visit 1), end of the study) were recorded in the participant's case report form. | From start of IP administration to end of the study visit (approximately 28 to 36 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Malignant and Benign Lesions Detected for Session 1 | At visit 1, after administration of 15 μg 68Ga-OPS202, a dynamic scan was performed in kidney region over first 30 minutes; static scans were performed from head to sub-inguinal region at 0.5, 1, 2 and 4 h post-injection. At visit 2, after administration of 50 μg 68Ga-OPS202, a static scan was performed from head to sub-inguinal region at 1 h post-injection. A previous somatostatin receptor scan had been performed within 6 months prior to Day 0. Lesions were classified into malignant and benign by readers. Lesion matching was performed between somatostatin receptor scan and 1 h-68Ga-OPS202 receptor scans at visit 1 and visit 2. Number of lesions for each organ/tissue and overall were calculated and absolute numbers reported. Two different read sessions were held to generate data sets for evaluation of target variables. Statistical comparisons were only feasible for those organs/ tissues that had sufficient participants with lesions detected. | 6 months prior to Day 0; and 1 hour post-injection on Day 0 and Day 21 | 
| Percentage of Participants With Lesion-Associated 68Ga-OPS202 Binding | Tumor contrast in PET imaging was determined by qualitative visual analysis. 68Ga-OPS202 binding was present if at least one lesion, regardless of nature, was detected within respective tissue location. Percentages were based on number of participants with available scan at corresponding time point. | At 0.5, 1, 2, and 4 hour post-injection on Day 0 and 1 hour post-injection on Day 21 | 
| Mean Maximum Standardized Uptake Value (SUVmax) of Malignant and Benign Lesions for Session 1 | At visit 1, after administration of 15 μg 68Ga-OPS202, a dynamic scan was performed in kidney region over the first 30 minutes (0-0.5 h); static scans were performed from head to sub-inguinal region at 0.5, 1, 2 and 4 h post-injection. At visit 2, after administration of 50 μg 68Ga-OPS202, a static scan was performed from head to sub-inguinal region at 1 h post-injection. A previous somatostatin receptor scan had been performed within 6 months prior to Day 0. Lesions were classified into malignant and benign lesion by the readers according to their experience. Lesion matching was performed between the somatostatin receptor scan and the 1 h-68Ga-OPS202 receptor scans at visit 1 and visit 2. The mean SUVmax of lesions (mean of all identified lesions in the lymph node and liver) was summarized by nature of the lesions (malignant, benign). Statistical comparisons were only feasible for those organs/ tissues that had sufficient participants with lesions detected. | 6 months prior to Day 0; and 1 hour post-injection on Day 0 and Day 21 | 
| Mean SUVmax of Malignant and Benign Lesions for Session 2 | The mean SUVmax of all identified lesions in the respective organ/tissue was determined. Statistical comparisons were only feasible for those organs/ tissues that had sufficient participants with lesions detected. | At 0.5, 1, 2, and 4 hour post-injection on Day 0 and 1 hour post-injection on Day 21 | 
| Mean SUVmax of Reference Tissues (RT) Region of Interests (ROIs) for Session 1 | Lesion matching was performed between somatostatin receptor scan and 1 h-68Ga-OPS202 receptor scans at visit 1 and visit 2. Mean SUVmax of all selected ROIs in corresponding RT was determined. Corresponding RTs were adjacent healthy regions (1 to 3 healthy regions were identified for each lesion), i.e. located in same organ and/or region as lesion. RTs were determined in tissue locations with malignant lesions only. ROIs were also selected in muscle tissue, which was used as an additional reference region. Statistical comparisons were only feasible for those organs/ tissues that had sufficient participants with lesions detected. | 6 months prior to Day 0; and 1 hour post-injection on Day 0 and Day 21 | 
| Mean SUVmax of RT for Session 2 | The mean SUVmax of all selected ROIs in the corresponding RT was determined. RTs were determined in tissue locations with malignant lesions only. ROIs were also selected in muscle tissue, which was used as an additional reference region. Statistical comparisons were only feasible for those organs/ tissues that had sufficient participants with lesions detected. | At 0.5, 1, 2, and 4 hour post-injection on Day 0 and 1 hour post-injection on Day 21 | 
| Mean Tumor Contrast (3D-SUV-R) of Malignant Lesions Compared to Pre-dose Scans for Session 1 | The tumor contrast, i.e. the SUV ratio for tumor (malignant lesion)-to-background (3D-SUV-R) of a single lesion was defined as: 3D-SUV-R = SUVmax of lesion / mean of SUVmax of corresponding RTs. Statistical comparisons were only feasible for those organs/ tissues that had sufficient participants with lesions detected. | 6 months prior to Day 0; and 1 hour post-injection on Day 0 and Day 21 | 
| The 3D-SUV-R of Malignant Lesions for Session 2 | The tumor contrast, i.e. the SUV ratio for 3D-SUV-R of a single lesion was defined as: 3D-SUV-R = SUVmax of lesion / mean of SUVmax of corresponding RTs. Statistical comparisons were only feasible for those organs/ tissues that had sufficient participants with lesions detected. | At 0.5, 1, 2, and 4 hour post-injection on Day 0 and 1 hour post-injection on Day 21 | 
| Percent Change in 3D-SUV-R of Malignant Lesions | The tumor contrast, i.e. the SUV ratio for 3D-SUV-R of a single lesion was defined as: 3D-SUV-R = SUVmax of lesion / mean of SUVmax of corresponding RT. For percent change, 68Ga-OPS202 receptor scan is compared to previous somatostatin receptor scan. | 6 months prior to Day 0; and 1 hour post-injection on Day 0 and Day 21 | 
| Number of Participants at Each Time Point With the Highest Observed Lesion Number Per Tissue Location | For determining a suitable time window for PET/CT with 68Ga-OPS202, the scans after administration of the 15 μg peptide dose were analyzed and the time point with the highest lesion number per tissue location and overall were determined. If the highest number of lesion was detected at more than one time point, the earliest time point was used. | At 0.5, 1, 2, and 4 hour post-injection on Day 0 | 
| Number of Participants at Each Time Point With the Highest Mean 3D-SUV-R Tumor Value | The time point with the highest mean 3D-SUV-R per tissue location were determined. If the highest mean 3D-SUV-R was detected at more than one time point, the earliest time point was used. | At 0.5, 1, 2, and 4 hour post-injection on Day 0 | 
| Best Diagnostic Scan Assessment | The assessment of every diagnostic 68Ga-OPS202 PET/CT scan of session 2 was rated by the reader from 1 to 5, where 1=worst diagnostic scan and 5=best diagnostic scan. Higher score indicates a better scan. | At 0.5, 1, 2, and 4 hour post-injection on Day 0 and 1 hour post-injection on Day 21 |