{"doi":"10.2967/jnumed.125.270411","title":"Phase 1 Study of [ <sup>177</sup> Lu]Lu-NeoB in Patients with Advanced Solid Tumors Overexpressing Gastrin-Releasing Peptide Receptor: Preliminary Safety and Dosimetry Results","abstract":"Gastrin-releasing peptide receptor (GRPR) is overexpressed in a range of tumor types, making it an attractive candidate for novel treatment approaches. NeoB binds to GRPR with high affinity and can be radiolabeled with <sup>68</sup>Ga ([<sup>68</sup>Ga]Ga-NeoB) for imaging or <sup>177</sup>Lu ([<sup>177</sup>Lu]Lu-NeoB, hereafter <sup>177</sup>Lu-NeoB) for therapy, making it suitable for theranostics. <b>Methods:</b> NeoRay is a prospective, phase 1/2a, open-label, multicenter, first-in-human study of <sup>177</sup>Lu-NeoB. Patients with selected advanced solid tumors with GRPR expression (confirmed by [<sup>68</sup>Ga]Ga-NeoB lesion uptake) were enrolled. Here, we report preliminary data (cutoff, April 29, 2024) from phase 1, which aimed to identify the maximum tolerated dose and/or recommended phase 2 dose of <sup>177</sup>Lu-NeoB. Patients were scheduled to receive at least 3 cycles of <sup>177</sup>Lu-NeoB at an interval of at least 6 wk. A Bayesian optimal interval design was used, with dose-escalation decisions based on dose-limiting toxicities (DLTs) during cycle 1 of each dose level. The primary endpoint was the incidence and nature of DLTs. Safety was assessed before and throughout each cycle. Dosimetry was assessed after the first administration. <b>Results:</b> Seventeen patients (median age, 65 y; 71% male) with advanced gastrointestinal stromal tumors, prostate cancer, glioblastoma, or breast cancer received <sup>177</sup>Lu-NeoB activities of 1.85 GBq (cycle 1) and then 5.55 GBq (cycles 2–4) (<i>n</i> = 3), 9.25 GBq (<i>n</i> = 9), or 11.1 GBq (<i>n</i> = 5). Four DLTs were observed in 3 patients who received 11.1 GBq: grade 3 anemia (<i>n</i> = 2), grade 4 neurologic decline (<i>n</i> = 1), and grade 3 encephalopathy (<i>n</i> = 1). No DLTs were observed at lower administered activities. Overall, 4 of 17 patients (23.5%) had treatment-related adverse events of grade 3 or higher. Among patients with at least 1 evaluable dosimetry measurement (<i>n</i> = 16), the mean absorbed dose coefficient was 0.10 Gy/GBq (SD, 0.056 Gy/GBq) in the kidneys, 0.055 Gy/GBq (SD, 0.039 Gy/GBq) in the pancreas, and 0.018 Gy/GBq (SD, 0.0076 Gy/GBq) in the red marrow. <b>Conclusion:</b><sup>177</sup>Lu-NeoB has a favorable organ dosimetry profile in patients with advanced solid tumors expressing GRPR, with a large safety margin compared with accepted external beam radiation therapy thresholds for organ toxicity. The maximum tolerated dose of <sup>177</sup>Lu-NeoB was identified as 9.25 GBq, and the recommended phase 2 dose for the phase 2a dose expansion is 9.25 GBq.","journal":"Journal of Nuclear Medicine","year":2025,"id":549179,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9656,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":636982,"name":"Lilja B. Sólnes","orcid":"0000-0002-2192-7425","position":1,"is_corresponding":false},{"id":821512,"name":"Astrid A.M. van der Veldt","orcid":"0000-0003-0446-1907","position":2,"is_corresponding":false},{"id":395857,"name":"Jeffrey Y.C. Wong","orcid":"0000-0001-9471-559X","position":3,"is_corresponding":false},{"id":672869,"name":"Luigi Aloj","orcid":"0000-0002-7452-4961","position":4,"is_corresponding":false},{"id":512173,"name":"Michael C. Heinrich","orcid":"0000-0003-3790-0478","position":5,"is_corresponding":false},{"id":1092355,"name":"Christopher T. Chen","orcid":"0000-0001-5848-961X","position":6,"is_corresponding":false},{"id":267038,"name":"Steven P. Rowe","orcid":"0000-0003-2897-4694","position":7,"is_corresponding":false},{"id":821507,"name":"Tessa Brabander","orcid":"0000-0002-8000-6490","position":8,"is_corresponding":false},{"id":1443377,"name":"Simon Pacey","orcid":"0000-0002-3303-7577","position":9,"is_corresponding":false},{"id":1443901,"name":"Paola Aimone","orcid":null,"position":10,"is_corresponding":false},{"id":1443378,"name":"Dhrubajyoti Pathak","orcid":"0000-0001-8094-3620","position":11,"is_corresponding":false},{"id":1443902,"name":"Lars Blumenstein","orcid":null,"position":12,"is_corresponding":false},{"id":1443379,"name":"Yongmin Liu","orcid":"0000-0002-1180-902X","position":13,"is_corresponding":false},{"id":539613,"name":"Andrei Iagaru","orcid":"0000-0003-0839-5329","position":14,"is_corresponding":false},{"id":1318396,"name":"Erik Mittra","orcid":null,"position":0,"is_corresponding":true}],"reference_count":24,"raw_metadata":null,"created_at":"2026-07-19T02:54:07.823422Z","pmid":"41344852","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}