{"doi":"10.1016/j.ebiom.2024.105496","title":"Safety and toxicity of Iopofosine I 131 (CLR 131) with external beam radiation therapy in recurrent or metastatic head and neck cancer: results of a phase 1 single-centre, open-label, single-arm, dose escalation and dose expansion study","abstract":"BACKGROUND: Re-irradiation of recurrent head and neck cancer (HNC) is often limited by tumour adherence to critical structures and/or radiation tolerance of critical normal tissues. Iopofosine I 131 (CLR 131) is a targeted small molecular phospholipid ether (PLE) drug conjugate that delivers iodine-131 selectively to tumour cells. We conducted a phase 1, single-centre, open-label study to determine whether CLR 131 given with reduced dose of external beam radiation therapy (EBRT) would be tolerable and feasible. METHODS: All participants received previous curative intent treatment with radiotherapy as primary or adjuvant treatment. Eligible participants demonstrated uptake of CLR 131 as indicated via single photon emission CT/CT (SPECT/CT) imaging following CLR 131 test dose. Participants received two therapeutic doses of CLR 131 (days 1 and 8) with SPECT/CT imaging performed to quantitate the biodistribution of CLR 131. Participants subsequently received EBRT to achieve the designated radiation dose (60-70 Gy). The primary endpoint was safety. This trial was registered with ClinicalTrials.gov, NCT04105543, and enrolment and follow-up are complete. FINDINGS: Twelve participants completed treatment with CLR 131 and EBRT. Eight participants experienced grade 4 non-DLT haematologic toxicities (2 anaemia, 8 leukopenia, 5 thrombocytopenia) at least probably attributed to CLR 131, consistent with the expected toxicity profile. Haematologic toxicities occurred during weeks 6-8 from the first dose of CLR 131 and resolved within three weeks without sequelae. There were no treatment-related grade 3-4 non-haematologic toxicities. INTERPRETATION: CLR 131 in combination with EBRT did not confer any safety concerns, and was tolerable in participants with recurrent/metastatic HNC. Myelosuppression was consistent with the known toxicity profile of CLR 131. FUNDING: National Institutes of HealthP50 DE026787, National Cancer InstituteP30 CA014520, National Institutes of Health1UL1TR002373, Cellectar, NCT04105543.","journal":"EBioMedicine","year":2024,"id":470121,"datarank":0.22796112011423575,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.020016965946252123,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.020016965946252123,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":3,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9649,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT04105543"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1050204,"name":"Adam Burr","orcid":null,"position":1,"is_corresponding":false},{"id":353967,"name":"Randall J. Kimple","orcid":"0000-0001-8336-8000","position":2,"is_corresponding":false},{"id":1154424,"name":"David P. Adam","orcid":"0000-0002-8282-6660","position":3,"is_corresponding":false},{"id":437916,"name":"Menggang Yu","orcid":"0000-0002-7904-3155","position":4,"is_corresponding":false},{"id":1304611,"name":"Shari M. Piaskowski","orcid":null,"position":5,"is_corresponding":false},{"id":1120649,"name":"Tiffany A. Glazer","orcid":"0000-0002-4223-9381","position":6,"is_corresponding":false},{"id":393179,"name":"Patrick M. Hill","orcid":"0000-0002-1208-0568","position":7,"is_corresponding":false},{"id":1120650,"name":"Gregory K. Hartig","orcid":"0000-0002-0302-7319","position":8,"is_corresponding":false},{"id":416695,"name":"Timothy M. McCulloch","orcid":"0000-0002-4678-9161","position":9,"is_corresponding":false},{"id":1121094,"name":"Aaron M. Wieland","orcid":null,"position":10,"is_corresponding":false},{"id":1304612,"name":"Diana Trask","orcid":null,"position":11,"is_corresponding":false},{"id":1304181,"name":"Kate Oliver","orcid":"0000-0002-0595-9080","position":12,"is_corresponding":false},{"id":1263236,"name":"Jarrod Longcor","orcid":"0000-0001-5890-4692","position":13,"is_corresponding":false},{"id":489866,"name":"Nicole Rogus‐Pulia","orcid":"0000-0001-7294-4180","position":14,"is_corresponding":false},{"id":458800,"name":"Steve Y. Cho","orcid":"0000-0003-2724-7778","position":15,"is_corresponding":false},{"id":451106,"name":"Bryan P. Bednarz","orcid":"0000-0002-7467-9816","position":16,"is_corresponding":false},{"id":259501,"name":"Paul M. Harari","orcid":"0000-0002-6207-5505","position":17,"is_corresponding":false},{"id":353966,"name":"Justine Y. Bruce","orcid":"0000-0002-5902-7430","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-19T02:05:36.656771Z","pmid":"39671752","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":[]}