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Abstract
BackgroundBudigalimab 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 methodsPatients 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.ResultsIn 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.ConclusionsThe 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.
Highlights
Programmed cell death protein 1 (PD-1), a cell surface protein predominantly expressed on activated T cells, is an inhibitory immune checkpoint receptor and important target for cancer therapy [1, 2]
For the head and neck squamous cell carcinoma (HNSCC) cohort, the first patient was screened on 4 January 2018, and the last patient on 22 January 2019; for the non-small cell lung cancer (NSCLC) cohort, the first patient was screened on 8 November 2017, and the last patient on 20 December 2018
Sufficient tumor samples for IHC analysis were obtained from 38 patients with HNSCC and 33 patients with NSCLC; 19 patients in the HNSCC cohort and 16 in the NSCLC cohort were PD-L1 +
Summary
Programmed cell death protein 1 (PD-1), a cell surface protein predominantly expressed on activated T cells, is an inhibitory immune checkpoint receptor and important target for cancer therapy [1, 2]. Unlike nivolumab and pembrolizumab, which are both of the immunoglobulin (Ig)G4 subclass, budigalimab is a humanized, recombinant IgG1 anti-PD-1 monoclonal antibody. It has been modified by point mutations (L234A, L235A) to reduce Fc receptor interactions and limit effector function. Eligible patients in the NSCLC expansion cohort had locally advanced or metastatic NSCLC, had previously experienced platinum-based therapy failure, and were naive to PD-1/PD-L1-targeting agents; in the HNSCC expansion cohort, patients had recurrent or metastatic disease that was not amenable to curative treatment with local or systemic therapy and were naive to PD-1/PD-L1-targeting agents For this first-in-human study, patients were not selected on the basis of the presence or absence of any particular driver oncogenic mutations nor on their PD-L1 status.
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