[177Lu]Lu-NeoB

Overview

[177Lu]Lu-NeoB (Lutetium-177 NeoBOMB1) is an investigational radioligand therapy that targets the gastrin‑releasing peptide receptor (GRPR), which is overexpressed in several solid tumors (e.g., prostate cancer, subsets of breast cancer, gastrointestinal stromal tumor [GIST], and glioblastoma). It uses a DOTA-chelated peptide GRPR antagonist (NeoB) labeled with the beta emitter 177Lu for targeted irradiation of GRPR‑positive lesions and is paired with the diagnostic PET agent [68Ga]Ga‑NeoB for patient selection and response assessment. Preclinical studies show high GRPR affinity, favorable biodistribution, and antitumor activity in xenograft models. Multiple early‑phase clinical trials are ongoing across tumor types; as of October 7, 2025, no peer‑reviewed human efficacy results for [177Lu]Lu‑NeoB have been published. (pubmed.ncbi.nlm.nih.gov)

Mechanism of action

NeoB is a high‑affinity GRPR antagonist radiolabeled with 177Lu via a DOTA chelator. After intravenous administration, [177Lu]Lu‑NeoB binds GRPR on tumor cells; the emitted beta particles from 177Lu deliver cytotoxic radiation to GRPR‑expressing tissues while allowing post‑therapy imaging. Antagonist ligands like NeoB demonstrate strong receptor binding with low internalization yet retain effective tumor targeting and retention suitable for therapy. (pubmed.ncbi.nlm.nih.gov)

Clinical development status

• First‑in‑human, phase I/IIa, open‑label study in advanced solid tumors with [68Ga]Ga‑NeoB‑positive lesions (NCT03872778) is ongoing; AACR 2024 reported it as a “trial in progress.” (novartis.com)
• Phase Ib studies in GRPR‑positive ER+/HER2‑ metastatic breast cancer:
• Combination with ribociclib and fulvestrant (NCT05870579; recruiting). (novartis.com)
• Combination with capecitabine, with a randomized phase II optimization component (NCT06247995; recruiting). (novartis.com)
• Phase Ib glioblastoma trial: combination with radiotherapy/temozolomide in newly diagnosed GBM and monotherapy in recurrent GBM (NCT05739942; recruiting). (novartis.com)
• A platform study in metastatic neuroendocrine prostate cancer assigns patients to PSMA-, SSTR2-, or GRPR‑targeted RLT based on predominant PET target expression and includes [177Lu]Lu‑NeoB (NCT06379217; recruiting). (trialstoday.org)

Efficacy

No peer‑reviewed human efficacy outcomes for [177Lu]Lu‑NeoB have been published to date. Ongoing trials list antitumor activity as an endpoint, and an AACR 2024 abstract confirms the first‑in‑human study is in progress. (novartis.com)

Selected preclinical efficacy: - In prostate cancer (PC‑3) xenografts, [177Lu]Lu‑NeoB significantly prolonged survival versus control without clear dose‑response beyond certain activity levels. (pubmed.ncbi.nlm.nih.gov) - In GIST xenografts, [177Lu]Lu‑NeoB achieved high, specific tumor uptake and durable tumor regressions at therapeutic doses. (pmc.ncbi.nlm.nih.gov)

Safety

No peer‑reviewed human safety results for [177Lu]Lu‑NeoB have been published. Trial objectives include safety, tolerability, radiation dosimetry, and organ exposure. (novartis.com)

Selected preclinical safety/dosimetry: - Repeat‑dose mouse studies showed kidneys as the principal dose‑limiting organ, with hydronephrosis/nephropathy at higher activities; pancreas and liver lacked clear histologic toxicity despite notable absorbed doses. Overall, treatment was generally tolerated. (pubmed.ncbi.nlm.nih.gov) - Additional preclinical work in PC‑3 xenografts noted survival benefits without evident pancreatic toxicity, though kidney changes were observed in some animals at late time points. (pubmed.ncbi.nlm.nih.gov)

Imaging and target expression

• Early human PET experience with [68Ga]Ga‑NeoB in prostate cancer and a phase IIa study in GIST demonstrate variable but often robust GRPR‑targeted uptake, supporting a theranostic workflow for selecting candidates for [177Lu]Lu‑NeoB therapy. (pubmed.ncbi.nlm.nih.gov)

Further reading

• Preclinical theranostic foundation for NeoB (J Nucl Med, 2017): https://pubmed.ncbi.nlm.nih.gov/27609789/ (pubmed.ncbi.nlm.nih.gov)
• Preclinical safety/dosimetry in mice (EJNMMI, 2022): https://link.springer.com/article/10.1007/s00259-022-05926-2 (link.springer.com)
• Preclinical prostate cancer efficacy (EJNMMI Res, 2023): https://pubmed.ncbi.nlm.nih.gov/37640941/ (pubmed.ncbi.nlm.nih.gov)
• Theranostic perspectives (preclinical and initial human PET with 68Ga‑NeoB; J Nucl Med, 2016): https://pubmed.ncbi.nlm.nih.gov/27493272/ (pubmed.ncbi.nlm.nih.gov)
• GIST phase IIa imaging with 68Ga‑NeoB (Eur J Nucl Med Mol Imaging, 2022): https://pubmed.ncbi.nlm.nih.gov/36428467/ (pubmed.ncbi.nlm.nih.gov)
• First‑in‑human [177Lu]Lu‑NeoB trial record (NCT03872778): https://www.novartis.com/clinicaltrials/study/nct03872778 (novartis.com)
• AACR 2024 “trial in progress” abstract: https://aacrjournals.org/cancerres/article/84/7_Supplement/CT290/742534/ (aacrjournals.org)
• Breast cancer phase Ib combo with ribociclib/fulvestrant (NCT05870579): https://www.novartis.com/clinicaltrials/study/nct05870579 (novartis.com)
• Breast cancer phase I/II combo with capecitabine (NCT06247995): https://www.novartis.com/clinicaltrials/study/nct06247995 (novartis.com)
• Glioblastoma phase Ib (NCT05739942): https://www.novartis.com/clinicaltrials/study/nct05739942; site example: https://www.uclahealth.org/clinical-trials/dose-finding-study-177lulu-neob-newly-diagnosed-glioblastoma (novartis.com)
• NEPC platform assigning RLT by target (includes [177Lu]Lu‑NeoB; NCT06379217): https://www.trialstoday.org/trial/NCT06379217 (trialstoday.org)

Notes - As of October 7, 2025, no peer‑reviewed human efficacy or safety outcomes for [177Lu]Lu‑NeoB have been published; findings above are based on preclinical studies and ongoing trial registrations/abstracts. (novartis.com)

Last updated: Oct 2025