First-in-human phase 1 study of budigalimab, an anti-PD-1 inhibitor, in patients with non-small cell lung cancer and head and neck squamous cell carcinoma

Cancer Immunol Immunother. 2022 Feb;71(2):417-431. doi: 10.1007/s00262-021-02973-w. Epub 2021 Jul 3.

Abstract

Background: Budigalimab is a humanized, recombinant immunoglobulin G1 monoclonal antibody targeting programmed cell death protein 1 (PD-1). We present the safety, efficacy, pharmacokinetic (PK), and pharmacodynamic data from patients enrolled in the head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) expansion cohorts of the phase 1 first-in-human study of budigalimab monotherapy (NCT03000257; registered 15 December 2016).

Patients and methods: Patients with recurrent/metastatic HNSCC or locally advanced/metastatic NSCLC naive to PD-1/PD-1-ligand inhibitors were enrolled; patients were not selected on the basis of oncogene driver mutations or PD-L1 status. Budigalimab was administered at 250 mg intravenously Q2W or 500 mg intravenously Q4W until disease progression/unacceptable toxicity. The primary endpoints were safety and PK; the secondary endpoint was efficacy. Exploratory endpoints included biomarker assessments.

Results: In total, 81 patients were enrolled (HNSCC: N = 41 [PD-L1 positive: n = 19]; NSCLC: N = 40 [PD-L1 positive: n = 16]); median treatment duration was 72 days (range, 1-617) and 71 days (range, 1-490) for the HNSCC and NSCLC cohorts, respectively. The most frequent grade ≥ 3 treatment-emergent adverse event was anemia (HNSCC: n = 9, 22%; NSCLC: n = 5, 13%). Both dosing regimens had comparable drug exposure and increased interferon gamma-induced chemokines, monokine induced by gamma interferon, and interferon-gamma-inducible protein 10. Objective response rates were 13% (90% CI, 5.1-24.5) in the HNSCC cohort and 19% (90% CI, 9.2-32.6) in the NSCLC cohort. Median progression-free survival was 3.6 months (95% CI, 1.7-4.7) and 1.9 months (95% CI, 1.7-3.7) in the HNSCC and NSCLC cohorts.

Conclusions: The safety, efficacy and biomarker profiles of budigalimab are similar to other PD-1 inhibitors. Development of budigalimab in combination with novel anticancer agents is ongoing.

Keywords: Budigalimab; Head and neck squamous cell cancer; Non-small cell lung cancer; PD-1 inhibitor.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Follow-Up Studies
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / pathology
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Squamous Cell Carcinoma of Head and Neck / drug therapy*
  • Squamous Cell Carcinoma of Head and Neck / immunology
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Tissue Distribution

Substances

  • Antibodies, Monoclonal, Humanized
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • budigalimab

Associated data

  • ClinicalTrials.gov/NCT03000257