{"doi":"10.21037/med-23-ab016","title":"AB016. Phase 2 clinical trial of PT-112 in patients with thymic epithelial tumors","abstract":"Background: PT-112 induces immunogenic cell death and stimulates an anti-cancer adaptive immune response. In a phase 1 trial, PT-112 has shown safety and durable clinical activity in patients (pts) with lung cancer and thymoma, with no increase in immune-mediated toxicity. We present preliminary results from an ongoing phase 2 study of PT-112 in pts with recurrent thymic epithelial tumors (TETs) (NCT05104736). Methods: Pts with progression after prior platinum receive PT-112 360 mg/m2 IV on days 1, 8 and 15 of a 28-day cycle. Prior history of autoimmunity (AI) or treatment with an immune checkpoint inhibitor (ICI) is permitted. Primary objective is to determine response rate. Effects of PT-112 on the peripheral immunome and the tumor immune microenvironment are analyzed. Results: Ten pts have been treated (median age: 54, thymoma: 5, prior AI: 3, median prior systemic therapies: 2.5). Among 9 pts evaluable for response, 8 (89%) had stable disease (including late-onset response in 1 case), and 1 (11%) had progressive disease. After a median potential follow-up of 7.4 months (mo) median progression-free survival is not reached in pts with thymoma and is 6.2 mo (95% CI: 1.8–7.9 mo) in thymic carcinoma. The most common treatment-related adverse events (TRAEs) are peripheral neuropathy (60%), anemia, fatigue and myalgias (each in 50%). Two (20%) pts experienced relapse of AI: ocular myasthenia (CRMP5 and CASPR2 antibody-positive) and immune cytopenias, both steroid-refractory, which responded to intravenous immunoglobulins and cyclosporine A, respectively. TRAE of immune cytopenia was associated with a T-cell infiltrate in the bone marrow. No new muscle-directed TRAEs have been observed. Findings in peripheral blood include an increase in activated CD4+ T cells, proliferative CD4, CD8, NK and regulatory T cells, and pro-inflammatory cytokines (including IFN-γ and TNF-α), and a decrease in immunosuppressive serum analytes (VEGF and TGF-β1). Paired tumor biopsies are being analyzed and results will be presented. Conclusions: PT-112 shows encouraging clinical activity in pts with recurrent TETs. In contrast to ICIs, no new irAEs have been observed. Immune analyses show evidence of immune activation. These early results support further evaluation of PT-112 in TETs.","journal":"Mediastinum","year":2023,"id":382901,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7809,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":580559,"name":"Shannon Swift","orcid":"0000-0002-7114-6926","position":1,"is_corresponding":false},{"id":239940,"name":"Renee N. Donahue","orcid":"0000-0002-6828-3073","position":2,"is_corresponding":false},{"id":1149778,"name":"Carolina Celades","orcid":null,"position":3,"is_corresponding":false},{"id":762303,"name":"Yo-Ting Tsai","orcid":"0000-0002-7556-1633","position":4,"is_corresponding":false},{"id":1120673,"name":"Molly A. 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Ames","orcid":"0000-0002-1124-5236","position":13,"is_corresponding":false},{"id":1149780,"name":"Brooke Raphael","orcid":null,"position":14,"is_corresponding":false},{"id":109203,"name":"Seth M. Steinberg","orcid":"0000-0002-8280-551X","position":15,"is_corresponding":false},{"id":239942,"name":"James L. Gulley","orcid":"0000-0002-6569-2912","position":16,"is_corresponding":false},{"id":239943,"name":"Jeffrey Schlom","orcid":"0000-0001-7932-4072","position":17,"is_corresponding":false},{"id":250451,"name":"Arun Rajan","orcid":"0000-0003-2776-3385","position":18,"is_corresponding":false},{"id":778754,"name":"Meredith J. McAdams","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T01:17:20.969491Z","pmid":null,"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":[]}