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

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

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).

Study Overview

• Status: Terminated
• Conditions: Breast Cancer; Small Cell Lung Cancer; Colorectal Cancer; Prostate Cancer; Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: [68Ga]-NeoBOMB1

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).

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria
    • Medical University Innsbruck Department of Nuclear Medicine
• France
  • La Tronche, France
    • University of Grenoble - Hopital Michallon, Service de Medicine Nucleaire
  • Pessac, France
    • University of Bordeaux, Unite TEP RECHERCHE - Hopital Xavier Arnozan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase II dosimetry group; 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; [68Ga]-radiolabeled bombesin peptide targeting Gastrin Releasing Peptide Receptors
Experimental: Phase II non-dosimetry group; 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; [68Ga]-radiolabeled bombesin peptide targeting Gastrin Releasing Peptide Receptors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Advanced Accelerator Applications

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2018
• Primary Completion (Actual): June 20, 2019
• Study Completion (Actual): July 5, 2019

Study Registration Dates

• First Submitted: October 21, 2018
• First Submitted That Met QC Criteria: October 26, 2018
• First Posted (Actual): October 30, 2018

Study Record Updates

• Last Update Posted (Actual): October 23, 2020
• Last Update Submitted That Met QC Criteria: October 22, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: [68Ga]-NeoBOMB1
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma
• Other Study ID Numbers: A005D-E01-201; 2017-003432-37 (EudraCT Number); CAAA503A12201 (Other Identifier: Novartis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No