Association of Baseline and Pharmacodynamic Biomarkers With Outcomes in Patients Treated With the PD-1 Inhibitor Budigalimab. Issue 3 (14th April 2022)

• Record Type: Journal Article
• Authors: Lambert, Stacie L.; Zhang, Chun; Guo, Claire; Turan, Tolga; Masica, David L.; Englert, Stefan; Fang, Yuni; Sheridan, James; McLaughlin, Robert Tyler; Tribouley, Catherine; Vosganian, Greg; Afar, Daniel
• Is Part Of: Journal of immunotherapy. Volume 45:Issue 3(2022)
• Page Start: 167
• Page End: 179
• Publication Date: 2022-04-14
• Subjects: budigalimab -- head and neck squamous cell carcinoma -- non-small cell lung cancer -- PD-1 inhibitor -- pharmacodynamics; Immunotherapy -- Periodicals; Immunotherapy -- Periodicals; Neoplasms -- therapy -- Periodicals; Electronic journals; Electronic journals; 615.37
• DOI: 10.1097/CJI.0000000000000408
• Languages: English
• ISSNs: 1524-9557

Abstract

Abstract : Budigalimab, a novel anti–PD-1 monoclonal antibody, demonstrated efficacy and biomarker pharmacodynamics in patients with head and neck squamous cell carcinoma (HNSCC) or non–small cell lung cancer (NSCLC) consistent with those reported by other PD-1 inhibitors. Herein are presented additional outcomes of biomarker analyses from the phase 1 study of budigalimab monotherapy in patients with HNSCC and NSCLC (NCT03000257). PD-1 inhibitor naive patients with advanced HNSCC (n=41) or NSCLC (n=40) received budigalimab intravenously at 250 mg every 2 weeks (Q2W) or 500 mg Q4W until progression. Archival tumor specimens were evaluated by immunohistochemistry for CD8 and tumor PD-1 ligand 1 (PD-L1) expression, RNA, and whole-exome sequencing. Serum and whole blood samples were acquired at baseline and at select on-treatment time points. As of October 2019, best overall response of 15% in HNSCC and 18% in NSCLC was observed in all treated patients; both cohorts reported responses in PD-L1 + and PD-L1 – tumors. Treatment with budigalimab was associated with increases in multiple soluble biomarkers including interferon gamma-induced chemokines. Expanded overall T-cell counts, total CD8 T-cell counts, and percentages of CD8 + CD45RA – CD62L – effector memory T cells were observed at cycle 1, day 15 in responders. Univariate analysis demonstrated an association between prolonged progression-free survival and higher tumor mutational burden/neoantigen load, smaller tumor size, lower platelet-lymphocyte ratios, lower CCL23, lower colony-stimulating factor 1, and lower interleukin-6 levels at baseline. The biomarker analysis presented herein identified additional early pharmacodynamic biomarkers associated with anti–PD-1 activity and improved clinical responses to budigalimab in patients with advanced HNSCC and NSCLC.