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

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

  • Oncologist. 2021 Sep;26(9):e1514-e1525. doi: 10.1002/onco.13817.
Kyriakos P Papadopoulos 1 Wael Harb 2 Cody J Peer 3 Qiong Hua 4 Siying Xu 4 Haolan Lu 4 Ni Lu 4 Yue He 4 Ting Xu 5 Ruiping Dong 6 John Gong 4 David Liu 4
Affiliations

Affiliations

  • 1 Clinical Research, South Texas Accelerated Research Therapeutics, San Antonio, Texas, USA.
  • 2 Horizon Oncology Research, LLC, Horizon BioAdvance, Lafayette, Indiana, USA.
  • 3 Clinical Pharmacology Program, National Cancer Institute, Bethesda, Maryland, USA.
  • 4 3D Medicines Co., Ltd., Sichuan, People's Republic of China.
  • 5 Alphamab Co., Ltd., Suzhou, People's Republic of China.
  • 6 Shanghai HaiHe Biopharma Pharmaceutical Co., Ltd., Shanghai, People's Republic of China.
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.

Keywords

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

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