A Phase I/II, Open-label, Multi-center Trial of [177Lu]Lu-NeoB in Combination With Capecitabine in Adult Patients With Gastrin Releasing Peptide Receptor Positive, Estrogen Receptor-positive, Human Epidermal Growth Factor Receptor-2 Negative Metastatic Breast Cancer After Progression on Previous Endocrine Therapy in Combination With a CDK4/6 Inhibitor.

In the phase I part, to determine the recommended doses (RD) and dosing regimens of [177Lu]Lu-NeoB in combination with capecitabine in adult patients with gastrin releasing peptide receptor positive, estrogen receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer after progression on previous endocrine therapy in combination with a CDK4/6 inhibitor. In the phase II part, to evaluate the preliminary anti-tumor activity of two different doses/regimens of [177Lu]Lu-NeoB in combination with capecitabine (dose optimization).

Start Date14 Aug 2024

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

NCT06379217 / RecruitingPhase 1

A Phase I, Open-label, Multi-center Exploratory Safety and Efficacy Study With PSMA, SSTR2 and GRPR Targeted Radioligand Therapy in Metastatic Neuroendocrine Prostate Cancer.

The purpose of this study is to evaluate the change in the expression of treatment targets on the surface of tumor cells (Prostate Specific Membrane Antigen (PSMA), Somatostatin Receptor 2 (SSTR2), and Gastrin Releasing Peptide Receptor (GRPR) between the start and after the completion of radioligand therapy (RLT). Study will use radioligand imaging (RLI) to determine predominantly expressed target on the surface of tumor cells. Based on predominant expression of target, corresponding RLT targeting PSMA, SSTR2, or GRPR RLT will be given for up to 6 cycles every 6 weeks as intravenous (i.v.) injection in participants with metastatic neuroendocrine prostate cancer (mNEPC).

Start Date29 Jul 2024

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

NCT05739942 / RecruitingPhase 1

Phase Ib Dose Finding Study Assessing Safety and Activity of [177Lu]Lu-NeoB in Combination With Radiotherapy and Temozolomide in Subjects With Newly Diagnosed Glioblastoma and as a Single Agent in Recurrent Glioblastoma

This study will investigate different doses of [177Lu]Lu-NeoB in combination with RT and TMZ in participants with newly diagnosed glioblastoma, with methylated or unmethylated promoter, to assess the safety and efficacy of [177Lu]Lu-NeoB in combination with the SoC and in recurrent glioblastoma as single agent, to identify the recommended dose and to also explore the safety of the PET imaging agent [68Ga]Ga-NeoB and characterize its uptake in the tumor area.

Start Date15 May 2024

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

100 Clinical Results associated with 177Lu-NeoBOMB1

100 Translational Medicine associated with 177Lu-NeoBOMB1

100 Patents (Medical) associated with 177Lu-NeoBOMB1

Literatures (Medical) associated with 177Lu-NeoBOMB1

01 Sep 2022·Journal of Nuclear Medicine

Substitution of l-Tryptophan by α-Methyl-l-Tryptophan in ¹⁷⁷Lu-RM2 Results in ¹⁷⁷Lu-AMTG, a High-Affinity Gastrin-Releasing Peptide Receptor Ligand with Improved In Vivo Stability

Article

Author: Günther, Thomas ; Wester, Hans-Jürgen ; Beck, Roswitha ; Felber, Veronika ; Deiser, Sandra

Theranostic applications targeting the gastrin-releasing peptide receptor (GRPR) have shown promising results. When compared with other peptide ligands for radioligand therapy, the most often used GRPR ligand, DOTA-Pip⁵-d-Phe⁶-Gln⁷-Trp⁸-Ala⁹-Val¹⁰-Gly¹¹-His¹²-Sta¹³-Leu¹⁴-NH₂ (RM2), may be clinically impacted by limited metabolic stability. With the aim of improving the metabolic stability of RM2, we investigated whether the metabolically unstable Gln⁷-Trp⁸ bond within the pharmacophore of RM2 can be stabilized via substitution of l-Trp⁸ by α-methyl-l-tryptophan (α-Me-l-Trp) and whether the corresponding DOTAGA analog might also be advantageous. A comparative preclinical evaluation of ¹⁷⁷Lu-α-Me-l-Trp⁸-RM2 (¹⁷⁷Lu-AMTG) and its DOTAGA counterpart (¹⁷⁷Lu-AMTG2) was performed using ¹⁷⁷Lu-RM2 and ¹⁷⁷Lu-NeoBOMB1 as reference compounds. Methods: Peptides were synthesized by solid-phase peptide synthesis and labeled with ¹⁷⁷Lu. Lipophilicity was determined at pH 7.4 (logD _7.4). Receptor-mediated internalization was investigated on PC-3 cells (37°C, 60 min), whereas GRPR affinity (half-maximal inhibitory concentration) was determined on both PC-3 and T-47D cells. Stability toward peptidases was examined in vitro (human plasma, 37°C, 72 ± 2 h) and in vivo (murine plasma, 30 min after injection). Biodistribution studies were performed at 24 h after injection, and small-animal SPECT/CT was performed on PC-3 tumor-bearing mice at 1, 4, 8, 24, and 28 h after injection. Results: Solid-phase peptide synthesis yielded 9%-15% purified labeling precursors. ¹⁷⁷Lu labeling proceeded quantitatively. Compared with ¹⁷⁷Lu-RM2, ¹⁷⁷Lu-AMTG showed slightly improved GRPR affinity, a similar low internalization rate, slightly increased lipophilicity, and considerably improved stability in vitro and in vivo. In vivo, ¹⁷⁷Lu-AMTG exhibited the highest tumor retention (11.45 ± 0.43 percentage injected dose/g) and tumor-to-blood ratio (2,702 ± 321) at 24 h after injection, as well as a favorable biodistribution profile. As demonstrated by small-animal SPECT/CT imaging, ¹⁷⁷Lu-AMTG also revealed a less rapid clearance from tumor tissue. Compared with ¹⁷⁷Lu-AMTG, ¹⁷⁷Lu-AMTG2 did not show any further benefits. Conclusion: The results of this study, particularly the superior metabolic stability of ¹⁷⁷Lu-AMTG, strongly recommend a clinical evaluation of this novel GRPR-targeted ligand to investigate its potential for radioligand therapy of GRPR-expressing malignancies.

01 Feb 2017·Journal of Nuclear MedicineQ1 · MEDICINE

⁶⁸Ga/¹⁷⁷Lu-NeoBOMB1, a Novel Radiolabeled GRPR Antagonist for Theranostic Use in Oncology

Q1 · MEDICINE

Article

Author: Dalm, Simone U ; Tedesco, Mattia ; Bakker, Ingrid L ; Nock, Berthold A ; Maina, Theodosia ; de Jong, Marion ; Konijnenberg, Mark W ; Doeswijk, Gabriela N ; de Blois, Erik ; Barbato, Donato ; Orlandi, Francesca

Because overexpression of the gastrin-releasing peptide receptor (GRPR) has been reported on various cancer types, for example, prostate cancer and breast cancer, targeting this receptor with radioligands might have a significant impact on staging and treatment of GRPR-expressing tumors. NeoBOMB1 is a novel DOTA-coupled GRPR antagonist with high affinity for GRPR and excellent in vivo stability. The purpose of this preclinical study was to further explore the use of NeoBOMB1 for theranostic application by determining the biodistribution of ⁶⁸Ga-NeoBOMB1 and ¹⁷⁷Lu-NeoBOMB1.METHODSPC-3 tumor-xenografted BALB/c nu/nu mice were injected with either approximately 13 MBq/250 pmol ⁶⁸Ga-NeoBOMB1 or a low (∼1 MBq/200 pmol) versus high (∼1 MBq/10 pmol) peptide amount of ¹⁷⁷Lu-NeoBOMB1, after which biodistribution and imaging studies were performed. At 6 time points (15, 30, 60, 120, 240, and 360 min for ⁶⁸Ga-NeoBOMB1 and 1, 4, 24, 48, 96, and 168 h for ¹⁷⁷Lu-NeoBOMB1) postinjection tumor and organ uptake was determined. To assess receptor specificity, additional groups of animals were coinjected with an excess of unlabeled NeoBOMB1. Results of the biodistribution studies were used to determine pharmacokinetics and dosimetry. Furthermore, PET/CT and SPECT/MRI were performed.RESULTSInjection of approximately 250 pmol ⁶⁸Ga-NeoBOMB1 resulted in a tumor and pancreas uptake of 12.4 ± 2.3 and 22.7 ± 3.3 percentage injected dose per gram (%ID/g) of tissue, respectively, at 120 min after injection. ¹⁷⁷Lu-NeoBOMB1 biodistribution studies revealed a higher tumor uptake (17.9 ± 3.3 vs. 11.6 ± 1.3 %ID/g of tissue at 240 min after injection) and a lower pancreatic uptake (19.8 ± 6.9 vs. 105 ± 13 %ID/g of tissue at 240 min after injection) with the higher peptide amount injected, leading to a significant increase in the absorbed dose to the tumor versus the pancreas (200 pmol, 570 vs. 265 mGy/MBq; 10 pmol, 435 vs. 1393 mGy/MBq). Using these data to predict patient dosimetry, we found a kidney, pancreas, and liver exposure of 0.10, 0.65, and 0.06 mGy/MBq, respectively. Imaging studies resulted in good visualization of the tumor with both ⁶⁸Ga-NeoBOMB1 and ¹⁷⁷Lu-NeoBOMB1.CONCLUSIONOur findings indicate that ⁶⁸Ga- or ¹⁷⁷Lu-labeled NeoBOMB1 is a promising radiotracer with excellent tumor uptake and favorable pharmacokinetics for imaging and therapy of GRPR-expressing tumors.

01 Jan 2017·Journal of Nuclear MedicineQ1 · MEDICINE

Theranostic Perspectives in Prostate Cancer with the Gastrin-Releasing Peptide Receptor Antagonist NeoBOMB1: Preclinical and First Clinical Results

Q1 · MEDICINE

Article

Author: Maina, Theodosia ; de Jong, Marion ; Krenning, Eric P ; Kulkarni, Harshad R ; Klette, Ingo ; Giarika, Athina ; Baum, Richard P ; Singh, Aviral ; Kaloudi, Aikaterini ; Nock, Berthold A ; Lymperis, Emmanouil

We recently introduced the potent gastrin-releasing peptide receptor (GRPR) antagonist ⁶⁸Ga-SB3 (⁶⁸Ga-DOTA-p-aminomethylaniline-diglycolic acid-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt), showing excellent tumor localizing efficacy in animal models and in patients. By replacement of the C-terminal Leu¹³-Met¹⁴-NH₂ dipeptide of SB3 by Sta¹³-Leu¹⁴-NH₂, the novel GRPR antagonist NeoBOMB1 was generated and labeled with different radiometals for theranostic use. We herein report on the biologic profile of resulting ^67/68Ga-, ¹¹¹In-, and ¹⁷⁷Lu-NeoBOMB1 radioligands in GRPR-expressing cells and mouse models. The first evidence of prostate cancer lesion visualization in men using ⁶⁸Ga-NeoBOMB1 and PET/CT is also presented.METHODSNeoBOMB1 was radiolabeled with ^67/68Ga, ¹¹¹In, and ¹⁷⁷Lu according to published protocols. The respective metalated species ^natGa-, ^natIn-, and ^natLu-NeoBOMB1 were also synthesized and used in competition binding experiments against [¹²⁵I-Tyr⁴]BBN in GRPR-positive PC-3 cell membranes. Internalization of ⁶⁷Ga-, ¹¹¹In-, and ¹⁷⁷Lu-NeoBOMB1 radioligands was studied in PC-3 cells at 37°C, and their metabolic stability in peripheral mouse blood was determined by high-performance liquid chromatography analysis of blood samples. Biodistribution was performed by injecting a ⁶⁷Ga-, ¹¹¹In-, or ¹⁷⁷Lu-NeoBOMB1 bolus (74, 74, or 370 kBq, respectively, 100 μL, 10 pmol total peptide ± 40 nmol Tyr⁴-BBN: for in vivo GRPR blockade) in severe combined immunodeficiency mice bearing PC-3 xenografts. PET/CT images with ⁶⁸Ga-NeoBOMB1 were acquired in prostate cancer patients.RESULTSNeoBOMB1 and ^natGa-, ^natIn-, and ^natLu-NeoBOMB1 bound to GRPR with high affinity (half maximal inhibitory concentration, 1-2 nM). ⁶⁷Ga-, ¹¹¹In-, and ¹⁷⁷Lu-NeoBOMB1 specifically and strongly bound on the cell membrane of PC-3 cells displaying low internalization, as expected for receptor antagonists. They showed excellent metabolic stability in peripheral mouse blood (>95% intact at 5 min after injection). After injection in mice, all 3 (⁶⁷Ga-, ¹¹¹In-, and ¹⁷⁷Lu-NeoBOMB1) showed comparably high and GRPR-specific uptake in the PC-3 xenografts (e.g., 30.6 ± 3.9, 28.6 ± 6.0, and >35 percentage injected dose per gram at 4 h after injection, respectively), clearing from background predominantly via the kidneys. During a translational study in prostate cancer patients, ⁶⁸Ga-NeoBOMB1 rapidly localized in pathologic lesions, achieving high-contrast imaging.CONCLUSIONThe GRPR antagonist radioligands ⁶⁷Ga-, ¹¹¹In-, and ¹⁷⁷Lu-NeoBOMB1, independent of the radiometal applied, have shown comparable behavior in prostate cancer models, in favor of future theranostic use in GRPR-positive cancer patients. Such translational prospects were further supported by the successful visualization of prostate cancer lesions in men using ⁶⁸Ga-NeoBOMB1 and PET/CT.

100 Deals associated with 177Lu-NeoBOMB1

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
GRPR Positive/ER Positive/HER2 Negative Breast Cancer	Phase 2	PT	Novartis Pharma AG	14 Aug 2024
GRPR Positive/ER Positive/HER2 Negative Breast Cancer	Phase 2	US	Advanced Accelerator Applications SA	14 Aug 2024
Advanced Malignant Solid Neoplasm	Phase 2	GB	Advanced Accelerator Applications SA	24 Jul 2019
Advanced Malignant Solid Neoplasm	Phase 2	AT	Advanced Accelerator Applications SA	24 Jul 2019
Advanced Malignant Solid Neoplasm	Phase 2	US	Advanced Accelerator Applications SA	24 Jul 2019
Advanced Malignant Solid Neoplasm	Phase 2	FR	Advanced Accelerator Applications SA	24 Jul 2019
Advanced Malignant Solid Neoplasm	Phase 2	DE	Advanced Accelerator Applications SA	24 Jul 2019
Advanced Malignant Solid Neoplasm	Phase 2	NL	Advanced Accelerator Applications SA	24 Jul 2019
Advanced Malignant Solid Neoplasm	Phase 2	ES	Advanced Accelerator Applications SA	24 Jul 2019
Neoplasms	Phase 2	-	Novartis Pharma AG	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis