{"doi":"10.1002/cncr.33145","title":"Phase 1 study of the immunotoxin LMB‐100 in patients with mesothelioma and other solid tumors expressing mesothelin","abstract":"BACKGROUND: LMB-100 is an antibody-toxin conjugate with an antimesothelin Fab linked to a 24-kilodalton portion of Pseudomonas exotoxin A with mutations that decrease immunogenicity. The objective of the current first-in-human phase 1 study was to determine the maximum tolerated dose (MTD) and safety in patients with advanced solid tumors expressing mesothelin. METHODS: Cohorts of 1 to 7 patients received intravenous LMB-100 at 7 dose levels from 40 µg/kg to 250 µg/kg intravenously on days 1, 3, and 5 of a 21-day cycle. RESULTS: Of the 25 patients accrued, 17 had mesothelioma, 3 each had ovarian or pancreatic cancer, and 2 patients had gastric cancer. Dose-limiting toxicities occurred in 2 of 4 patients treated at a dose of 250 µg/kg (capillary leak syndrome) and in 3 of 7 patients treated at a dose of 170 µg/kg (creatinine increase). The MTD of LMB-100 was 140 µg/kg. Of the 10 patients with mesothelioma who were treated at doses of 170 µg/kg or 140 µg/kg, 8 had stable disease and 2 developed progressive disease. Peak LMB-100 plasma concentrations were dose-dependent during cycle 1. The development of antidrug antibodies decreased LMB-100 blood levels in 8 of 21 patients (38%) who received cycle 2 and 9 of 11 patients (81.8%) who received cycle 3. CONCLUSIONS: The MTD for single-agent LMB-100 was found to be 140 µg/kg given on a schedule of every other day for 3 doses every 3 weeks. Although less immunogenic than the first-generation antimesothelin immunotoxin SS1P, the majority of patients developed antidrug antibodies after 2 cycles, indicating that LMB-100 has limited antitumor efficacy as a single agent. Phase 2 studies of LMB-100 plus pembrolizumab currently are ongoing for patients with mesothelioma and lung cancer. LAY SUMMARY: Mesothelin, a cell surface antigen, is an attractive target for cancer therapy given its limited expression in normal human tissues and high expression in many human cancers. LMB-100 is a recombinant antimesothelin immunotoxin consisting of a humanized antimesothelin antibody fragment fused to a truncated Pseudomonas exotoxin A. In the current study, the authors determined the safety, maximum tolerated dose, and pharmacokinetics of LMB-100, as well as the generation of antidrug antibodies. Ongoing phase 2 clinical trials are evaluating the combination of LMB-100 plus pembrolizumab in patients with treatment-refractory mesothelioma and non-small cell lung cancer.","journal":"Cancer","year":2020,"id":60435,"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":62,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9008,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":301531,"name":"Christine Alewine","orcid":"0000-0003-1661-0957","position":1,"is_corresponding":false},{"id":319527,"name":"Idrees Mian","orcid":null,"position":2,"is_corresponding":false},{"id":318653,"name":"Anna Spreafico","orcid":"0000-0002-3034-3042","position":3,"is_corresponding":false},{"id":318654,"name":"Lillian L. Siu","orcid":"0000-0002-3500-0540","position":4,"is_corresponding":false},{"id":88330,"name":"Carlos Gomez‐Roca","orcid":"0000-0002-8043-2529","position":5,"is_corresponding":false},{"id":318655,"name":"Jean‐Pierre Delord","orcid":"0000-0001-7305-5561","position":6,"is_corresponding":false},{"id":105066,"name":"Antoîne Italiano","orcid":"0000-0002-8540-5351","position":7,"is_corresponding":false},{"id":226643,"name":"Ulrik Lassen","orcid":"0000-0002-3865-4574","position":8,"is_corresponding":false},{"id":91591,"name":"Jean‐Charles Soria","orcid":"0000-0001-9597-0701","position":9,"is_corresponding":false},{"id":319528,"name":"Rastilav Bahleda","orcid":null,"position":10,"is_corresponding":false},{"id":253875,"name":"Anish Thomas","orcid":"0000-0003-3293-3115","position":11,"is_corresponding":false},{"id":109203,"name":"Seth M. Steinberg","orcid":"0000-0002-8280-551X","position":12,"is_corresponding":false},{"id":109199,"name":"Cody J. Peer","orcid":"0000-0001-9395-3473","position":13,"is_corresponding":false},{"id":109200,"name":"William D. Figg","orcid":"0000-0003-2428-5613","position":14,"is_corresponding":false},{"id":318656,"name":"Gerhard Niederfellner","orcid":"0000-0001-5487-2929","position":15,"is_corresponding":false},{"id":319529,"name":"Valérie Meresse Naegelen","orcid":null,"position":16,"is_corresponding":false},{"id":289051,"name":"Ira Pastan","orcid":"0000-0002-9223-0270","position":17,"is_corresponding":false},{"id":311178,"name":"Raffit Hassan","orcid":"0000-0002-4012-3633","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T21:08:47.852401Z","pmid":"32870522","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":[]}