Envafolimab
(Synonyms: ASC 22; KN 035) 目录号 : GC66344
Envafolimab (ASC 22; KN 035) 是人源化的单域抗PD-L1 抗体的重组蛋白。 Envafolimab 是由抗 PD-L1 结构域与人 IgG1 抗体的 Fc 片段融合而成。Envafolimab 阻断 PD-L1 和 PD-1 之间的相互作用，IC50 值为 5.25 nm。Envafolimab 显示出抗肿瘤活性。Envafolimab 具有研究实体瘤的潜力。
Cas No.:2102192-68-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Envafolimab (ASC 22; KN 035) is a recombinant protein of a humanized single-domain anti- PD-L1 antibody. Envafolimab is created by a fusion of the of anti-PD-L1 domain with Fc fragment of human IgG1 antibody. Envafolimab blocks interaction between PD-L1 and PD-1 with an IC50 value of 5.25 nm. Envafolimab shows antitumor activity. Envafolimab has the potential for the research of solid tumors[1][2][3].
Envafolimab (0-2.51 nM) induces T-cell cytokine (IFN-γ) production in a dose- and time-dependent manner[3].
Envafolimab (0.18-0.92 mg/kg; i.p.; four times over 2 weeks) shows antitumor activity with a half-life of ~72 h in NOD-SCID mice (A375 cells)[3].
| Cas No. | 2102192-68-5 | SDF | Download SDF |
| 别名 | ASC 22; KN 035 | ||
| 分子式 | 分子量 | ||
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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Envafolimab: First Approval
Drugs 2022 Feb;82(2):235-240.PMID:35122636DOI:10.1007/s40265-022-01671-w.
Envafolimab (®) is a subcutaneously (SC) administered single domain anti-programmed death ligand 1 (PD-L1) antibody being developed for the treatment of various solid tumours and chronic hepatitis B in China, and for soft tissue sarcomas and biliary tract cancer in the USA. Single-domain antibodies are more soluble and more rapidly penetrate tissues than full monoclonal antibodies, enabling SC administration. Based on the results of a pivotal phase II trial, SC Envafolimab was recently approved in China for the treatment of adult patients with previously-treated microsatellite instability-high (MSI-H) or deficient MisMatch Repair (dMMR) advanced solid tumours. This article summarizes the milestones in the development of Envafolimab leading to this first approval.
Subcutaneous Envafolimab monotherapy in patients with advanced defective mismatch repair/microsatellite instability high solid tumors
J Hematol Oncol 2021 Jun 21;14(1):95.PMID:34154614DOI: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, https://clinicaltrials.gov/ct2/show/NCT03667170 .
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.PMID:33973293DOI:10.1002/onco.13817.
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.
Envafolimab - first PD-1/PD-L1 antibody to be administered by subcutaneous injection for microsatellite instability-high or deficient mismatch repair advanced solid tumors
Expert Opin Biol Ther 2022 Oct;22(10):1227-1232.PMID:36124972DOI:10.1080/14712598.2022.2125799.
Introduction: Programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors mobilize and activate the anti-tumor activity of the immune system by blocking the inhibitory effects of the PD-1/PD-L1 signaling pathway in T cells. Several anti-PD-1 or -PD-L1 monoclonal antibodies have been approved for the treatment of advanced solid tumors. However, most of immune checkpoint inhibitors (ICIs) are administered via intravenous infusion, which is inconvenient and leads to unsatisfactory patient compliance in the treatment process. Therefore, subcutaneous Envafolimab is a potential treatment modality for advanced solid tumors. Area covered: A phase I clinical trial showed that the safety and pharmacokinetic profiles of Envafolimab were similar to those of other traditional antibodies. Additionally, clinical findings from a phase II trial revealed that Envafolimab monotherapy exhibited satisfactory clinical therapeutic effects and no significant adverse events in patients with microsatellite instability-high/deficient mismatch Repair (MSI-H/dMMR) solid tumors who failed at least one line of prior systemic therapy. Expert opinion: Subcutaneous Envafolimab may serve as a more convenient and acceptable treatment modality than those approved PD-1/PD-L1 inhibitors for patients with an advanced solid tumor, which may revolutionize the modes of immunotherapy in the future.
Phase I study of Envafolimab (KN035), a novel subcutaneous single-domain anti-PD-L1 monoclonal antibody, in Japanese patients with advanced solid tumors
Invest New Drugs 2022 Oct;40(5):1021-1031.PMID:35932387DOI:10.1007/s10637-022-01287-7.
Envafolimab is the first and only globally approved subcutaneously injectable PD-L1 antibody. This open-label, multicenter Phase 1 trial assessed the safety, tolerability, pharmacokinetic (PK) profile, and efficacy of Envafolimab as a single agent in Japanese patients with advanced solid tumors. In the dose-escalation phase, 10 patients received subcutaneous (SC) Envafolimab QW at 1.0 mg/kg, 2.5 mg/kg and 5.0 mg/kg. In the dose-expansion phase, 16 patients were treated at 2.5 or 5.0 mg/kg Q2W in part-1 and 9 patients received SC Envafolimab 300 mg Q4W in part-2. No dose-limiting toxicities (DLTs) were reported. Envafolimab was well tolerated and no new safety signals were identified compared with other marketed products of the same class. Three patients reported Grade ≥ 3 envafolimab-related treatment-emergent adverse events (TEAE), including adrenal insufficiency, cerebral infarction, and immune-mediated enterocolitis. Envafolimab demonstrated dose-proportional increases in area under the time-concentration curve (AUC) and maximum serum concentration (Cmax). The overall response rate (ORR) was 11.4% (n = 4) and disease control rate (DCR) was 34.3% (n = 12). Consistent with that observed in other Envafolimab Phase 1 trials and approved PD-1/PD-L1 inhibitors, the safety profile of SC Envafolimab in Japanese patients with advanced solid tumors was well tolerated with efficacy comparable to IV administered treatments. Pharmacokinetics data and preliminary anti-tumor response support dose regimens with longer dosing intervals (Q2W or Q4W). As such, Envafolimab offers patients a more convenient treatment option than currently available intravenously administered PD-1/PD-L1 inhibitors. CLINICALTRIALS.GOV IDENTIFIER: NCT03248843(August 14, 2017).