Pilot Study of Avelumab in Thymic Epithelial Tumors

Division Of Basic Sciences - Nci

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Abstract

Thymic epithelial tumors (TETs; composed of thymomas and thymic carcinomas) are programmed death-ligand 1 (PD-L1)-expressing tumors with low tumor mutation burden, and particularly with thymomas, defective immune tolerance that increases the risk of paraneoplastic autoimmunity. We have previously demonstrated activity of avelumab with an increased incidence of skeletal and cardiac muscle inflammation in a small cohort of patients with recurrent thymoma (Rajan A, JITC, 2019). This study is designed to confirm the safety and activity of avelumab and evaluate cyclosporine A (CsA) for secondary prophylaxis against immune myositis and isolated troponin elevation. Patients with recurrent TETs and no active autoimmune disease were eligible and received avelumab 10 mg/kg intravenously every two weeks. Patients developing non-life-threatening immune-related adverse events (irAEs) resumed avelumab after appropriate management. CsA was used for secondary prophylaxis against musculoskeletal irAEs at the lowest effective dose. Preliminary results from 22 evaluable participants have confirmed clinical activity of avelumab [thymoma cohort: partial response: 2 (17%), stable disease: 10 (83%); thymic carcinoma cohort: partial response: 2 (20%), stable disease: 6 (60%), progressive disease: 2 (20%)]. After a median potential follow-up of 18.6 months, median progression-free survival for participants with thymoma was 6.4 months (95% CI: 3.7 months - not estimable) and 14.7 months (95% CI: 1.3 months - not estimable) for participants with thymic carcinoma. irAEs occurred in 12 (52%) participants (thymoma 58%, thymic carcinoma 45%). The most common irAEs of any grade included myositis (17%), sicca syndrome (13%), myocarditis and thyroiditis (9% each). Avelumab rechallenge with CsA secondary prophylaxis was feasible in three of four (75%) participants with myositis with no further issues. irAEs caused treatment discontinuation in three (13%) participants. No treatment-related deaths occurred. All patients had high pre-treatment soluble PD-L1 levels compared with healthy donors. Low baseline B-cell counts correlated with clinical response and occurrence of some irAEs. Taken together, we have confirmed the safety and clinical activity of avelumab in patients with recurrent TETs and shown the ability of CsA to successfully prevent recurrent episodes of immune myositis upon avelumab rechallenge. This study completed enrollment in 2025 and full results are expected to be published in 2026.