{"doi":"10.1093/oncolo/oyaf373","title":"Phase Ib study of berzosertib, carboplatin, gemcitabine, and pembrolizumab in patients with squamous nonsmall lung cancer (ETCTN 10313)","abstract":"BACKGROUND: Berzosertib is a potent and selective inhibitor of ataxia telangiectasia Rad3-related and potentiates cisplatin and gemcitabine in lung xenografts. We hypothesized that berzosertib plus carboplatin, gemcitabine, and pembrolizumab is tolerable and active in newly diagnosed advanced squamous NSCLC. METHODS: This phase Ib clinical trial studied berzosertib 135 mg/m2 IV Days 2 and 9 with carboplatin AUC 4-5 Day 1, gemcitabine 800 mg/m2 Days 1 and 8, and pembrolizumab 200 mg Day 1, of a 3-week cycle. Primary endpoint was the recommended phase II dose (RP2D). Antitumor activity and pharmacokinetics were secondary endpoints. RESULTS: Twelve patients were enrolled and treated. Two of six patients at DL 1 (berzosertib 135 mg/m2, carboplatin area under the curve (AUC) 5, gemcitabine 800 mg/m2, and pembrolizumab 200 mg) experienced a dose-limiting toxicity: grade 5 gastric hemorrhage upon intractable nausea and vomiting; grade 3 neutropenia resulting in treatment delay. None of 6 patients experienced a DLT at DL-1 (berzosertib 135 mg/m2, carboplatin AUC 4, gemcitabine 800 mg/m2, and pembrolizumab 200 mg). The most common grade ≥3 TRAEs were leukopenia (75%), neutropenia (67%), anemia (58%), thrombocytopenia (33%), and lymphopenia (33%). Berzosertib and gemcitabine exposure did not correlate with the highest grade cycle 1 toxicity. Five of eleven evaluable patients (46%) experienced partial response. CONCLUSION: In newly diagnosed advanced squamous non-small cell lung cancer (NSCLC), berzosertib 135 mg/m2, carboplatin AUC 4, gemcitabine 800 mg/m2, and pembrolizumab 200 mg was the RP2D, which was both tolerable and associated with activity. This study did not proceed to phase II upon discontinuation of berzosertib development. Clinicaltrials.gov Identifier: NCT04216316.","journal":"The Oncologist","year":2025,"id":548390,"datarank":0.10876211857566623,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.004790041491674418,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.004790041491674418,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9476,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT04216316"]},"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":1441577,"name":"Benjamin Schluger","orcid":"0000-0002-0453-8110","position":1,"is_corresponding":false},{"id":105025,"name":"Hong Wang","orcid":"0000-0003-0477-2908","position":2,"is_corresponding":false},{"id":557789,"name":"James Ohr","orcid":"0000-0002-7037-6404","position":3,"is_corresponding":false},{"id":1442079,"name":"Daniel P. Petro","orcid":null,"position":4,"is_corresponding":false},{"id":1032596,"name":"Alexander D. Fuld","orcid":null,"position":5,"is_corresponding":false},{"id":1207529,"name":"Benjamin Herzberg","orcid":"0000-0002-3253-3106","position":6,"is_corresponding":false},{"id":1441578,"name":"Richa Dawar","orcid":"0000-0001-8846-1263","position":7,"is_corresponding":false},{"id":363242,"name":"Jorge J. Nieva","orcid":"0000-0003-1605-4719","position":8,"is_corresponding":false},{"id":281347,"name":"Jimmy Ruiz","orcid":"0000-0002-7242-3315","position":9,"is_corresponding":false},{"id":1166587,"name":"Susan M. Christner","orcid":null,"position":10,"is_corresponding":false},{"id":743347,"name":"Julianne L. Holleran","orcid":"0000-0002-3738-8200","position":11,"is_corresponding":false},{"id":576133,"name":"Christopher J. Bakkenist","orcid":"0000-0001-9672-0886","position":12,"is_corresponding":false},{"id":646455,"name":"Steven D. Gore","orcid":"0000-0002-3649-8758","position":13,"is_corresponding":false},{"id":414176,"name":"Jan H. Beumer","orcid":"0000-0002-8978-9401","position":14,"is_corresponding":false},{"id":230279,"name":"Liza C. Villaruz","orcid":"0000-0001-7456-523X","position":0,"is_corresponding":true}],"reference_count":11,"raw_metadata":null,"created_at":"2026-07-19T02:53:58.530220Z","pmid":"41206673","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":[]}