[68Ga]-NeoBOMB1 Imaging in Patients With Malignancies Known to Overexpress Gastrin Releasing Peptide Receptor (GRPR)

Study Overview
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Brief Summary
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This was a Phase II, multi-center, open label, single dose study in patients with tumor types known to overexpress Gastrin-Releasing Peptide Receptor (GRPR), including breast, prostate, colorectal, Non-Small Cell Lung Cancer (NSCLC) and Small-Cell Lung Cancer (SCLC).

Detailed Description
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A total of 50 subjects were planned for the study (10 subjects for the dosimetry group and 40 subjects for the non dosimetry group). In total, 22 subjects were screened for eligibility and 19 subjects were enrolled (2 subjects in the dosimetry group and 17 subjects in the non dosimetry group).

Official Title
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Phase II Study of Preliminary Diagnostic Performance of [68Ga]-NeoBOMB1 in Adult Patients With Malignancies Known to Overexpress Gastrin Releasing Peptide Receptor (GRPR)

Conditions
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Breast Cancer, Prostate Cancer, Colorectal Cancer, Non Small Cell Lung Cancer, Small Cell Lung Cancer

Intervention / Treatment
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* Drug: [68Ga]-NeoBOMB1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be at least 18 years of age Subjects must have signed and dated an informed consent prior to any study-specific procedures Subjects with histologically-confirmed tumor for whom a recent biopsy (not older than 6-months old) has been performed. Dosimetry group: luminal breast cancer, adenocarcinoma of the prostate Non-dosimetry group: luminal breast cancer, adenocarcinoma of the prostate, small cell lung cancer, non-small cell lung cancer, colorectal carcinoma At least one malignant lesion detected via functional or morphological imaging (PET combined to appropriate tracer according to tumor type, CT, MRI) within 3 months prior to [68Ga]-NeoBOMB1 administration The Eastern Cooperative Oncology (ECOG) performance status 0-2. Subjects must agree to use highly effective methods of contraception (female partners of male participants should use highly effective methods of contraception) during the trial. Exclusion Criteria: renal insufficiency or an eGFR <50 ml/min/1.73m2 hematological toxicity grade > 2 (Toxicity Grading Scale in vaccine clinical trials) participation in any other investigational trial within 30 days of study entry subjects with positive pregnancy test (urine dipstick), and/or currently breast-feeding concurrent severe illness or clinically relevant trauma within 2 weeks before the administration of the investigational product that might preclude study completion or interfere with study results concurrent bladder outflow obstruction or unmanageable urinary incontinence known or expected hypersensitivity to [68Ga]-NeoBOMB1 or any excipient present in [68Ga]-NeoBOMB1 any condition that precludes raised arms position prior administration of a radiopharmaceutical within a period corresponding to 8 half-lives of the radionuclide history of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study design included a dosimetry and non-dosimetry groups and with the following tumor types: Breast Cancer: dosimetry and non-dosimetry groups Prostate Cancer: dosimetry and non-dosimetry groups Colorectal cancer: non-dosimetry group Non-Small Cell Lung Cancer (NSCLC): non-dosimetry group Small-Cell Lung Cancer (SCLC): non-dosimetry group All data presentations were to be presented primarily by the overall population but were also to be repeated split by tumor type where relevant. Some presentations were also to be repeated split by whether or not the patient was found to have tumors bearing GRPR expression according to cytology and/or histopathology findings.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase II dosimetry group<br>All eligible participants were to receive recommended dose of [68Ga]-NeoBOMB1 of 3 Mega Becquerel (MBq)/Kg (+/- 10%) [but not more than 250 and not less than 150 MBq. The maximum peptide mass administered was 50 microgram (µg)]. | Drug: [68Ga]-NeoBOMB1<br>* [68Ga]-radiolabeled bombesin peptide targeting Gastrin Releasing Peptide Receptors<br>|
| Experimental: Phase II non-dosimetry group<br>All eligible participants were to receive recommended dose of [68Ga]-NeoBOMB1 of 3 Mega Becquerel (MBq)/Kg (+/- 10%) [but not more than 250 and not less than 150 MBq. The maximum peptide mass administered was 50 microgram (µg)]. | Drug: [68Ga]-NeoBOMB1<br>* [68Ga]-radiolabeled bombesin peptide targeting Gastrin Releasing Peptide Receptors<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-Dosimetry Group: Standard Uptake Value (SUV) Max by Timepoint and Lesion Location | Targeting properties of [68Ga]-NeoBOMB1 were to be evaluated by semi-quantitatively assessing radiotracer uptake at lesion level, identified via PET Imaging. The SUVmean and SUVmax (g/mL) of each lesion were to be calculated and reported by lesion location with summary statistics at all imaging time points. SUV was to be calculated overall and split by GRPR positive and negative patients, as well as by tumor type. Only descriptive analysis performed. | [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.05 (only applicable for the Prostate Group), 1.50 and 2.50 hours) | 
| Dosimetry Group: Standard Uptake Value (SUV) Mean by Timepoint and Lesion Location | Targeting properties of [68Ga]-NeoBOMB1 were to be evaluated by semi-quantitatively assessing radiotracer uptake at lesion level, identified via PET Imaging. The SUVmean and SUVmax (g/mL) of each lesion were to be calculated and reported by lesion location with summary statistics at all imaging time points. SUV was to be calculated overall and split by GRPR positive and negative patients, as well as by tumor type. Only descriptive analysis performed. | [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.15, 1.00, 2.00 and 4.00 hours) | 
| Dosimetry Group: Standard Uptake Value (SUV) Max by Timepoint and Lesion Location | Targeting properties of [68Ga]-NeoBOMB1 were to be evaluated by semi-quantitatively assessing radiotracer uptake at lesion level, identified via PET Imaging. The SUVmean and SUVmax (g/mL) of each lesion were to be calculated and reported by lesion location with summary statistics at all imaging time points. SUV was to be calculated overall and split by GRPR positive and negative patients, as well as by tumor type. Only descriptive analysis performed. | [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.15, 1.00, 2.00 and 4.00 hours) | 
| Dosimetry Group: Evaluation of Percentage of Injected Dose Reaching the Target (TACs) in Tumors | For patients included in the dosimetry group, the percentage of injected dose per gram of tissue (%ID/g) reaching tumor lesions was to be calculated using the acquired PET images at each time point. The resulting TACs were to be summarized descriptively. | [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.15, 1.00, 2.00 and 4.00 hours) | 
| Dosimetry Group: Evaluation of Percentage of Injected Dose Reaching the Target (TACs) in Organs | For patients included in the dosimetry group, the percentage of injected dose per gram of tissue (%ID/g) reaching source organs was to be calculated using the acquired PET images at each time point. The resulting TACs were to be summarized descriptively. | [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.15, 1.00, 2.00 and 4.00 hours) | 
| Number of Lesions Detected by [68Ga]-NeoBOMB1 | The preliminary targeting properties of [68Ga]-NeoBOMB1 were to be assessed by summarizing the number of lesions identified by Positron Emission Tomography (PET) overall and split by GRPR positive and negative patients, as well as by tumor type. Only descriptive analysis performed. | [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 | 
| Number of Participants With Lesions Detected by [68Ga]-NeoBOMB1 Per Location | The preliminary targeting properties of [68Ga]-NeoBOMB1 were to be assessed by summarizing the location of lesions identified by PET overall and split by GRPR positive and negative patients, as well as by tumor type. Only descriptive analysis performed. | [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 | 
| Non-Dosimetry Group: Standard Uptake Value (SUV) Mean by Timepoint and Lesion Location | Targeting properties of [68Ga]-NeoBOMB1 were to be evaluated by semi-quantitatively assessing radiotracer uptake at lesion level, identified via PET Imaging. The SUVmean and SUVmax (g/mL) of each lesion were to be calculated and reported by lesion location with summary statistics at all imaging time points. SUV was to be calculated overall and split by GRPR positive and negative patients, as well as by tumor type. Only descriptive analysis performed. | [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.05 (only applicable for the Prostate Group), 1.50 and 2.50 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dosimetry Group: Urinary Excretion of [68Ga]-NeoBOMB1 (Vd) | Urine samples were collected for activity-based pharmacokinetics characterization in the dosimetry group. Vd was to be listed and summarized using descriptive statistics. | [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 | 
| Treatment Emergent Adverse Events Profile | Treatment-emergent adverse events (TEAEs) were collected from first dosing (single administration, Day 1) up to last follow-up visit or until the event has resolved to baseline grade or better or the event was assessed stable by the investigator or the patient was lost to follow-up or withdrew consent. The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Grade 3/4/5 TEAEs, Serious Adverse Event TEAEs, Interruption of [68Ga]-NeoBOMB1 Due to Any TEAEs and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis performed. | From first dosing (single administration, Day 1) up to last follow-up visit or until the event has resolved to baseline grade or better or the event was assessed stable by the investigator or the patient was lost to follow-up or withdrew consent. | 
| Number of Lesions Detected by Conventional Imaging | The preliminary targeting properties of [68Ga]-NeoBOMB1 were to be assessed by summarizing the number of lesions identified by Positron Emission Tomography (PET) overall and split by GRPR positive and negative patients, as well as by tumor type. The number of lesions identified by aforementioned PET imaging were to be compared with the number of lesions identified by the comparable conventional imaging. Only descriptive analysis performed. | Conventional imaging collected within 3 months prior to study entry up to [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 | 
| Number of Participants With Lesions Detected by Conventional Imaging Per Location | The preliminary targeting properties of [68Ga]-NeoBOMB1 were to be assessed by summarizing the location of lesions identified by PET overall and split by GRPR positive and negative patients, as well as by tumor type. The location of lesions identified by aforementioned PET imaging were to be compared with the location of lesions identified by the comparable conventional imaging. Only descriptive analysis performed. | Conventional imaging collected within 3 months prior to study entry up to [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 | 
| Lesion-level Analyses of Diagnostics by [68Ga]-NeoBOMB1 Compared With Conventional Imaging | At lesion level, overall, positive, and negative agreement of [68Ga]-NeoBOMB1 were to be calculated based on the aforementioned tabulations as follows: Overall agreement = 100% x (Double positive + Double negative) / total number of lesions identified by either imaging proceduresg Positive agreement = 100% x Double positive / (Double positive + Comparator single positive) Negative agreement = 100% x Double negative / (Double negative + Comparator single negative). | Conventional imaging collected within 3 months prior to study entry up to [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 | 
| Patient-level Analyses of Diagnostics by [68Ga]-NeoBOMB1 Compared With Conventional Imaging | At patient level, positive agreement was defined as the proportion of subjects with at least one lesion detected by conventional imaging in the specified location that also have at least one lesion detected by [68Ga]-NeoBOMB1. Overall agreement was defined as the proportion of subjects with at least one lesion detected in either imaging in the specified location that also have at least one lesion detected by [68Ga]-NeoBOMB1. | Conventional imaging collected within 3 months prior to study entry up to [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 | 
| Organ-level Analyses of Diagnostics by [68Ga]-NeoBOMB1 Compared to Histological Evidence | The diagnostic performance of [68Ga]-NeoBOMB1 to GRPR overexpressing malignancies (lesions) was to be compared with cytology and/or histopathology findings from archival and/or recent biopsy specimens. Since the biopsy was performed on 1 lesion (collected either in primary or in metastatic tumors), a direct link may not be possible in case of multiple lesions per organ identified on [68Ga]-NeoBOMB1-PET. In this event, the determination of positive versus negative lesions on [68Ga]-NeoBOMB1-PET was done at organ level, i.e., if any lesion is positive in that organ, then the organ was to be considered positive. The sensitivity was to be calculated as follows: Sensitivity = 100% x True positive / (True positive + False negative). | Biopsy specimen collected within 6 months prior to study entry up to [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 | 
| Dosimetry Group: Absorbed Dose in Target Organs | The absorbed dose in target organs and the effective radiation dose were to be summarized with descriptive statistics. Lesion number were assigned by dosimetry expert. | [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 | 
| Dosimetry Group: Effective Whole-body Dose | The effective radiation dose was to be summarized with descriptive statistics. | [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 | 
| Dosimetry Group: Half-life of [68Ga]-NeoBOMB1 in Blood (T^1/2) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization in the dosimetry group. The half-lives of distribution (T^1/2 alpha) and elimination phases (T^1/2 beta) were to be listed and summarized using descriptive statistics. | [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 | 
| Dosimetry Group: Time of Maximum Observed Drug Concentration Occurrence (Tmax) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization in the dosimetry group. Tmax was to be listed and summarized using descriptive statistics. | [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 | 
| Dosimetry Group: Observed Maximum Plasma Concentration (Cmax) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization in the dosimetry group. Cmax was to be listed and summarized using descriptive statistics. | [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 | 
| Dosimetry Group: Area Under the Plasma Concentration-time Curve From the Time 0 to the Last Observed Quantifiable Concentration (AUC(0-t)) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization in the dosimetry group. AUC(0-t) was to be listed and summarized using descriptive statistics. | [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 | 
| Dosimetry Group: AUC(0-t) Divided by the Dose Administered (AUC(0-t)/D) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization in the dosimetry group. AUC(0-t)/D was to be listed and summarized using descriptive statistics. | [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 | 
| Dosimetry Group: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUCinf) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization in the dosimetry group. AUC(0-inf) was to be listed and summarized using descriptive statistics. | [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 | 
| Dosimetry Group: Total Systemic Clearance for Intravenous Administration (CL) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization in the dosimetry group. CL was to be listed and summarized using descriptive statistics. | [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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[68Ga]-NeoBOMB1