Subcutaneous envafolimab monotherapy in patients with advanced defective mismatch repair/microsatellite instability high solid tumors

• Published in: Journal of hematology and oncology Vol. 14; no. 1; pp. 1 - 95
• Main Authors: Li, Jian, Deng, Yanhong, Zhang, Weijie, Zhou, Ai-Ping, Guo, Weijian, Yang, Jianwei, Yuan, Ying, Zhu, Liangjun, Qin, Shukui, Xiang, Silong, Lu, Haolan, Gong, John, Xu, Ting, Liu, David, Shen, Lin
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 21.06.2021; BioMed Central; BMC
• Subjects: Adverse events; Antibodies; Cancer; Cancer therapies; Care and treatment; Colorectal cancer; Colorectal carcinoma; Complications and side effects; Disease control; dMMR/MSI-H; Drug dosages; Envafolimab; Gastric cancer; Hematology; Immune checkpoint; Injection; Intravenous administration; Laboratories; Medical prognosis; Metastases; Metastasis; Microsatellite instability; Mismatch repair; Monoclonal antibodies; Mutation; Oncology; Patients; PD-L1; PD-L1 protein; Population; Rapid Communication; Response rates; Safety; Solid tumors; Subcutaneous injection; Survival; Tumors; Viral antibodies; United States > US
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-021-01095-1

Background Monoclonal antibodies targeting programmed death ligand 1 (PD-L1) signaling currently approved for defective mismatch repair (dMMR)/microsatellite instability high (MSI-H) tumors must be delivered by intravenous infusion. Envafolimab, a humanized single-domain anti-PD-L1 antibody fused to an Fc fragment, represents a potential advance because it can be conveniently administered subcutaneously. Methods This open-label, single-arm, phase 2 study evaluated the efficacy and safety of envafolimab in patients with previously treated advanced dMMR/MSI-H tumors from 25 clinical sites across China. Adults with histologically confirmed locally advanced or metastatic malignant dMMR/MSI-H solid tumors received weekly 150 mg subcutaneous envafolimab injections in a 28-day treatment cycle. The primary efficacy endpoint was the objective response rate (assessed by a blinded independent review committee). Secondary efficacy outcomes were disease control rate, duration of response, progression-free survival, and overall survival. Results One hundred and three patients (65 with colorectal cancer, 18 with gastric cancer, and 20 with other solid tumors) were enrolled. Median follow-up was 11.5 months. The objective response rate was 42.7% (95% confidence interval [CI] 33.0-52.8), and the disease control rate was 66.0% (95% CI 56.0-75.1). Median duration of response was not reached; the duration of response rate at 12 months was 92.2% (95% CI 77.5-97.4). Median progression-free survival was 11.1 months (95% CI 5.5 to not evaluable). Overall survival at 12 months was 74.6% (95% CI 64.7-82.1). Sixteen patients (16%) had at least one grade 3 or 4 related treatment-emergent adverse event. No grade 5 treatment-emergent adverse events related to envafolimab were reported. Injection site reactions, all grade 1-2, were reported in nine patients (9%), but there were no infusion reactions. Eight patients (8%) had grade 3 or 4 immune-related adverse events. Conclusions This is the first pivotal phase 2 study to examine the efficacy and safety of a single-domain immune checkpoint antibody in the treatment of cancer. Envafolimab was effective and had acceptable safety in the treatment of previously treated advanced dMMR/MSI-H solid tumors. As the first single-domain PD-L1-targeting antibody administered by rapid subcutaneous injection, envafolimab has the potential to be a significant advance in the treatment of cancer. Trial registration ClinicalTrials.gov, NCT03667170. Registered 10 September 2018--Retrospectively registered, Keywords: Envafolimab, PD-L1, dMMR/MSI-H, Subcutaneous injection