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

Phase 2

Terminated

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

Interventions: Drug: [68Ga]-NeoBOMB1

Registration Number: NCT03724253

Lead Sponsor: Advanced Accelerator Applications

Brief Summary: 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: 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).

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 19

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase II dosimetry group	[68Ga]-NeoBOMB1	All eligible participants were to receive recommended dose of \[68Ga\]-NeoBOMB1 of 3 Mega Becquerel (MBq)/Kg (+/- 10%) \[but not more than 250 and not less than 150 MBq. The maximum peptide mass administered was 50 microgram (µg)\].
Phase II non-dosimetry group	[68Ga]-NeoBOMB1	All eligible participants were to receive recommended dose of \[68Ga\]-NeoBOMB1 of 3 Mega Becquerel (MBq)/Kg (+/- 10%) \[but not more than 250 and not less than 150 MBq. The maximum peptide mass administered was 50 microgram (µg)\].

Primary Outcome Measures

Name	Time	Method
Number of Lesions Detected by [68Ga]-NeoBOMB1	[68Ga]-NeoBOMB1 PET imaging acquired at Day 1	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.
Number of Participants With Lesions Detected by [68Ga]-NeoBOMB1 Per Location	[68Ga]-NeoBOMB1 PET imaging acquired at Day 1	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.
Non-Dosimetry Group: Standard Uptake Value (SUV) Mean by Timepoint and Lesion Location	[68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.05 (only applicable for the Prostate Group), 1.50 and 2.50 hours)	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.
Non-Dosimetry Group: Standard Uptake Value (SUV) Max by Timepoint and Lesion Location	[68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.05 (only applicable for the Prostate Group), 1.50 and 2.50 hours)	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.
Dosimetry Group: Standard Uptake Value (SUV) Mean by Timepoint and Lesion Location	[68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.15, 1.00, 2.00 and 4.00 hours)	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.
Dosimetry Group: Standard Uptake Value (SUV) Max by Timepoint and Lesion Location	[68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.15, 1.00, 2.00 and 4.00 hours)	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.
Dosimetry Group: Evaluation of Percentage of Injected Dose Reaching the Target (TACs) in Tumors	[68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.15, 1.00, 2.00 and 4.00 hours)	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.
Dosimetry Group: Evaluation of Percentage of Injected Dose Reaching the Target (TACs) in Organs	[68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.15, 1.00, 2.00 and 4.00 hours)	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.

Secondary Outcome Measures

Name	Time	Method
Treatment Emergent Adverse Events Profile	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.	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.
Number of Lesions Detected by Conventional Imaging	Conventional imaging collected within 3 months prior to study entry up to [68Ga]-NeoBOMB1 PET imaging acquired at Day 1	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.
Number of Participants With Lesions Detected by Conventional Imaging Per Location	Conventional imaging collected within 3 months prior to study entry up to [68Ga]-NeoBOMB1 PET imaging acquired at Day 1	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.
Lesion-level Analyses of Diagnostics by [68Ga]-NeoBOMB1 Compared With Conventional Imaging	Conventional imaging collected within 3 months prior to study entry up to [68Ga]-NeoBOMB1 PET imaging acquired at Day 1	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).
Patient-level Analyses of Diagnostics by [68Ga]-NeoBOMB1 Compared With Conventional Imaging	Conventional imaging collected within 3 months prior to study entry up to [68Ga]-NeoBOMB1 PET imaging acquired at Day 1	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.
Organ-level Analyses of Diagnostics by [68Ga]-NeoBOMB1 Compared to Histological Evidence	Biopsy specimen collected within 6 months prior to study entry up to [68Ga]-NeoBOMB1 PET imaging acquired at Day 1	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).
Dosimetry Group: Absorbed Dose in Target Organs	[68Ga]-NeoBOMB1 PET imaging acquired at Day 1	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.
Dosimetry Group: Effective Whole-body Dose	[68Ga]-NeoBOMB1 PET imaging acquired at Day 1	The effective radiation dose was to be summarized with descriptive statistics.
Dosimetry Group: Half-life of [68Ga]-NeoBOMB1 in Blood (T^1/2)	[68Ga]-NeoBOMB1 PET imaging acquired at Day 1	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.
Dosimetry Group: Time of Maximum Observed Drug Concentration Occurrence (Tmax)	[68Ga]-NeoBOMB1 PET imaging acquired at Day 1	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.
Dosimetry Group: Observed Maximum Plasma Concentration (Cmax)	[68Ga]-NeoBOMB1 PET imaging acquired at Day 1	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.
Dosimetry Group: Area Under the Plasma Concentration-time Curve From the Time 0 to the Last Observed Quantifiable Concentration (AUC(0-t))	[68Ga]-NeoBOMB1 PET imaging acquired at Day 1	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.
Dosimetry Group: AUC(0-t) Divided by the Dose Administered (AUC(0-t)/D)	[68Ga]-NeoBOMB1 PET imaging acquired at Day 1	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.
Dosimetry Group: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUCinf)	[68Ga]-NeoBOMB1 PET imaging acquired at Day 1	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.
Dosimetry Group: Total Systemic Clearance for Intravenous Administration (CL)	[68Ga]-NeoBOMB1 PET imaging acquired at Day 1	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.
Dosimetry Group: Urinary Excretion of [68Ga]-NeoBOMB1 (Vd)	[68Ga]-NeoBOMB1 PET imaging acquired at Day 1	Urine samples were collected for activity-based pharmacokinetics characterization in the dosimetry group. Vd was to be listed and summarized using descriptive statistics.

Trial Locations

Locations (3): 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