Back to Search
Start Over
<scp>First-in-Human</scp> Phase I Study of Envafolimab, a Novel Subcutaneous <scp>Single-Domain Anti-PD-L1</scp> Antibody, in Patients with Advanced Solid Tumors
- Source :
- Oncologist
- Publication Year :
- 2021
- Publisher :
- Oxford University Press (OUP), 2021.
-
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.
- Subjects :
- Male
0301 basic medicine
Cancer Research
medicine.medical_specialty
Urology
Antibodies, Monoclonal, Humanized
B7-H1 Antigen
03 medical and health sciences
Subcutaneous injection
Route of administration
0302 clinical medicine
Pharmacokinetics
Refractory
Neoplasms
medicine
Humans
In patient
Immune Checkpoint Inhibitors
Aged
Dose-Response Relationship, Drug
biology
business.industry
Clinical Trial Results
Anti pd 1
Antibodies, Monoclonal
Phase i study
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
biology.protein
Female
Antibody
business
Subjects
Details
- ISSN :
- 1549490X and 10837159
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- The Oncologist
- Accession number :
- edsair.doi.dedup.....0f752d381ffe5d46a68a748dbed37371