Association of Baseline and Pharmacodynamic Biomarkers With Outcomes in Patients Treated With the PD-1 Inhibitor Budigalimab.
J Immunother
; 45(3): 167-179, 2022 04 01.
Article
in En
| MEDLINE
| ID: mdl-35034046
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.
Full text:
1
Database:
MEDLINE
Main subject:
Carcinoma, Non-Small-Cell Lung
/
Head and Neck Neoplasms
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Lung Neoplasms
/
Antineoplastic Agents
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
J Immunother
Journal subject:
ALERGIA E IMUNOLOGIA
/
NEOPLASIAS
/
TERAPEUTICA
Year:
2022
Type:
Article