First-in-Human Phase I Study of Envafolimab, a Novel Subcutaneous Single-Domain Anti-PD-L1 Antibody, in Patients with Advanced Solid Tumors

Abstract

Lessons learned: Subcutaneous injection was an effective route of administration for envafolimab with a favorable pharmacokinetic profile in patients with previously treated advanced solid tumors. Subcutaneous envafolimab was well tolerated and had durable antitumor activity at a wide range of doses and schedules. Envafolimab has the potential to be a more convenient option than currently approved intravenous PD-1/PD-L1 inhibitors.

Background: Envafolimab is a novel fusion of a humanized single-domain PD-L1 antibody and human IgG1 Fc fragment formulated for subcutaneous injection. This study explored the safety and feasibility of subcutaneous administration of envafolimab as an alternative to intravenous administration of PD-1/PD-L1 inhibitors in the treatment of advanced, refractory solid tumors.

Methods: This was a first-in-human, open-label phase I trial. In a dose-escalation phase, patients received subcutaneous envafolimab 0.01-10 mg/kg once weekly following a modified 3+3 design. In a dose-exploration phase, patients received subcutaneous envafolimab 300 mg once every 4 weeks.

Results: Twenty-eight patients were enrolled (dose escalation n = 18, dose exploration n = 10, median age 66 years; 71% male; ECOG performance score = 0 [21%] or 1 [79%]). No dose-limiting toxicities or injection-site reactions were reported. Envafolimab demonstrated dose-proportional increases in area under the time-concentration curve and maximum plasma concentration. Median time to maximum plasma concentration was 4-7 days. In the dose-exploration phase, terminal half-life was 14 days after dose 1 in cycle 1 and 23 days at steady state. Three patients experienced a confirmed partial response.

Conclusion: Subcutaneous envafolimab had a favorable safety and pharmacokinetic profile, with promising preliminary antitumor activity in patients with advanced solid tumors.

Trial registration: ClinicalTrials.gov NCT02827968.

Keywords: Advanced solid tumors; Anti-PD-L1; Envafolimab.

© AlphaMed Press; the data published online to support this summary are the property of the authors.

Figures

Figure 1

Waterfall plot of tumor reduction from baseline during the dose‐escalation and dose‐exploration phases (n = 18). Abbreviations: GI, gastrointestinal; IHBT, intrahepatic biliary tract; NSCLC, non‐small cell lung cancer; PD, progressive disease; PR, partial response; Q4W, once every 4 weeks; QW, once weekly; SD, stable disease.

Figure 2

Relationship between natural log‐transformed dose and Cmax(A) and AUClast(B). Slopes were calculated by nonlinear regression analysis. Abbreviations: AUClast, area under the curve until the last measurement; Cmax, maximum plasma concentration.

Figure 3

Effect of subcutaneous injection site on first‐dose dose‐normalized Cmax(A) Or dose‐normalized AUClast(B). Abbreviations: AUClast, area under the curve until the last measurement; Cmax, maximum plasma concentration.

Figure 4

Dose‐normalized steady‐state serum concentrations of envafolimab in patients without and with antidrug antibodies. Abbreviations: ADA, antidrug antibody; Cmin,ss, minimum serum concentration at steady state.