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).
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).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
19
\[68Ga\]-radiolabeled bombesin peptide targeting Gastrin Releasing Peptide Receptors
Medical University Innsbruck Department of Nuclear Medicine
Innsbruck, Austria
University of Grenoble - Hopital Michallon, Service de Medicine Nucleaire
La Tronche, France
University of Bordeaux, Unite TEP RECHERCHE - Hopital Xavier Arnozan
Pessac, France
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.
Time frame: [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.
Time frame: [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.
Time frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.05 (only applicable for the Prostate Group), 1.50 and 2.50 hours)
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.
Time frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.05 (only applicable for the Prostate Group), 1.50 and 2.50 hours)
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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.
Time frame: [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.
Time frame: [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.
Time frame: [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.
Time frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.15, 1.00, 2.00 and 4.00 hours)
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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: [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.
Time frame: [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.
Time frame: [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.
Time frame: [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.
Time frame: [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.
Time frame: [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.
Time frame: [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.
Time frame: [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.
Time frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1
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.
Time frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1