The first subcutaneous injection of PD-L1 is coming!Domestic primary research PD-L1 inhibitor Genwali single anti-batch list!Establish MSI-H / DMMR treatment new benchmark

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The first subcutaneous injection of PD-L1 is coming!Domestic primary research PD-L1 inhibitor Genwali single anti-batch list!Establish MSI-H / DMMR treatment new benchmark

2021-11-27 18:08:21 50 ℃

* For medical professionals reading reference only

China immunotherapy Adds weapon!

November 25, 2021, Chinese State Drug Administration (NMPA) approved by priority review and approval procedures of the PD-L1 monoclonal antibody inhibitors Enwo Li (En Weida, envafolimab) listed for unresectable or metastatic treatment of adult patients with advanced solid tumors highly microsatellite instability (MSI-H) or deficient mismatch repair genes (dMMR), including past after fluoropyrimidine, oxaliplatin and irinotecan advanced disease progression after irinotecan treatment other disease progression in patients with advanced solid tumors of colorectal cancer patients as well as after previous treatment and no satisfactory alternative treatment options.

The original research drugs for our PD-L1 monoclonal antibody, and have a unique way on the international subcutaneous injection, and other similar products currently on the market has obvious advantages compared to its convenient mode of administration and good efficacy and safety for the Chinese cancer patients to bring a new immunotherapy razor, so this is approved the listing of great significance.

(NMPA) Screenshot

The approval is based on the significant clinical benefit II study Enwo Li monoclonal antibody therapy MSI-H / dMMR tumor patients exhibited entity registered as an innovative drug, Enwo Li monoclonal antibody in Phase II study data announced shortly after, the rapid inclusion in the priority review and was recently approved, officially entered into the Chinese MSI-H / dMMR the field of advanced solid tumors for patients to bring a new treatment option and hope for survival, but also led China towards precise tumor immunotherapy further treatment of the era.

Focus MSI-H / dMMR, Enwo Li monoclonal antibody fully demonstrated the therapeutic value of immunization

MSI-H / dMMR is currently one of biomarkers to predict the efficacy of immunotherapy most important, it has been applied to a variety of advanced solid tumors populations, including immune therapeutic advantages, including gastric and colorectal cancer screening. 2021 V1 latest National Comprehensive Cancer Network (NCCN) guidelines to enhance the recommended level of gastric MSI / MMR detection, it is recommended that all newly diagnosed patients with gastric cancer should be MSI polymerase chain reaction (PCR) detection or mismatch repair protein (MMR ) immunohistochemical (IHC) detection [1]. En Woli monoclonal antibody approved based on the results of this phase II clinical study domestic, Enwo Li mAb alone (150mg QW administration) for 103 cases of MSI-H / dMMR or more second-line treatment of patients with solid tumors objective response rate (ORR) was 42.7%, including 65 cases of colorectal cancer, the ORR 43.1%. The median progression-free survival (PFS) was 11.1 months, and 1-year overall survival (OS) rate was 74.6% [2]. The study results demonstrate Enwo Li monoclonal antibody has good therapeutic value in MSI-H / dMMR patients with advanced solid tumors.

Table 1 Enwo Li mAb treatment efficacy in patients with solid tumors China MSI-H / dMMR

Clinical trials of the first individual Enwo Li mAb of the I [3] explores more convenient mode of administration, dose to explore the basis of the original, for 10 subjects using monoclonal subcutaneous 300mg Enwo Li administration (Q4W) manner once every 4 weeks. After the first administration, the drug half-life of about 15 days after administration of 5 cycles, a steady state drug half-life is 23 days. Further, the area and the lower peak plasma concentration profile in humans mAbs Enwo Li not influenced by the site of injection, the simulation results pharmacokinetics of support, able to follow a fixed dose, or 300 mg Q3W of 400 mg Q4W drug program, greatly improving the convenience of the extent of drug use.

The world's first subcutaneous injection of PD-L1 monoclonal antibody, help achieve management of chronic diseases

Unlike other immune checkpoint inhibitors are, the world's first monoclonal Enwo Li subcutaneous PD-L1 inhibitor, it is taken subcutaneous administration, it is stable at room temperature, to limit the injection site than less, can be easily accomplished administration. Currently marketed PD-1 / PD-L1 inhibitor after intravenous injection, but also to be seen whether there infusion reactions, and therefore takes longer. And breaking the monoclonal antibody Enwo Li PD-1 / PD-L1 inhibitor mode of administration intravenous infusion of the past, subcutaneous mode of administration avoids the occurrence of infusion reactions, greatly shortening the length of time of administration, either follow-up in the management of patients, or medical resources, it is showing its unique advantages.

Subcutaneous injection can not only bring even the patient's home medication at the nearest hospital for medical treatment significantly reduced travel and related expenses arising from Lawton, but also reduces the monoclonal antibody administered intravenously PD-1 / PD-L1 brought risk of adverse reactions. For elderly patients with cancer and cancer patients with poor physical score, in the pursuit of efficacy, urgently need to be able to take into account the safety, tolerability and ease of immune drugs. En Woli monoclonal antibody is ideal for patients unable to take intravenous injections, medication can improve patient compliance and improve patient quality of life.

At present, for exploring Enwo Li monoclonal antibody dosing interval prolonged, and further increases the convenience Enwo Li monoclonal antibody. En Woli monoclonal unique advantages in terms of administration, the target tumor as a long-term management of chronic diseases, with landmark significance.

En Woli monoclonal antibody security control, escort patients with medication

Enwali combined with good tolerance and safety, the safety data of the clinical study of the Navoli monocramics show [2], 103 cases of MSI-H / DMMR solid tumor patients, 16 patients (15.5%) The adverse events occurring between 3-4 and drug-related treatment occurred (TEAE), no research drug related level 5 TEAE. In addition, it is worth noting that in the study, the incidence of immune pneumonia was 0%, and the incidence of colitis colitis was 0%. At the same time, Enwali monoclonims were administered subcutaneous injection, and the incidence of adverse reactions was 0%; the incidence of injection portions was only 8.7%, all of which were 1-2, no relevant serious adverse events or cause permanent stopping drugs. Time happens. Table 2 Enwali monochastic treatment China MSI-H / DMMR solid tumor patient safety

Immune-related pneumonia, enteritis, etc. is one of the possible adverse events (AE) that may occur in other PD-1 / PD-L1 monoclonal use, although it is not common, there is a fatal threat, due to non-small cell lung cancer (NSCLC) patients Often accepted immunotherapy, the evidence of many immune pneumonia in the real world, a report of 6 medical centers in North Carlona, ​​North Carlona, ​​were received by 6 medical centers in North Carlona, ​​2004, received three kinds of PD-1 / CTLA-4 The lung cancer cases (NSCLC accounted for 93.%, including 61.7%, squamous cell carcinoma) [4] showed that 17.5% of cases were displaced by IRAE due to IRAE displaced immunotherapy drugs. Approximately 10% of patients occur in immunoid pneumonia during treatment, and the median occurrence time is 52 days after diagnosis. For more severe immune pneumonia, clinically treated tricky, usually need to stop immunotherapy and use hormone control, which not only affects patient anti-tumor treatment, but also increases the additional costs produced by the treatment AE. The listing of Enwolley monocontrol will effectively avoid the occurrence of related adverse reactions.

As can be seen from the study of II, Enwali mono-injection not only shows long-lasting anti-tumor activity in patients with MSI-H / DMMR solid tumor, but also superior convenience, and also showing its controllable safety.

New immunotherapy weapons, Enwo Lili dedicated to patients with multiple benefits

With the arrival of tumor immunotherapy, MSI-H / DMMR as the effect of tumor immunotherapy efficacy prediction factor is increasing, and has become the focus of clinical attention. Enwali single anti-injection is the world's first subcutaneous injection of PD-L1 inhibitors, and clinical research data confirmed that its anti-tumor efficacy and controllability of China MSI-H / DMMR advanced solid tumor can be Previous MSI-H / DMMR in patients with last line of standard treatment failed, patients with a new treatment, also brought hope for more MSI-H / DMMR patients.

Therefore, Enwolley monocompanism is expected to lead immunotherapy into the era of precision medication. After approves listing and entering China's clinical application, with the use of domestic clinical continuous accumulation of immunotherapy drugs, future or will bring more The new exploration direction, such as the combination of various drugs based on its good security, the exploration of the administration cycle, the optimization of the patient's treatment, etc., will enrich the new opportunity of immunotherapy. It is expected that the listing of Enwali single anti-injection has a place in the future development of immunotherapy, raising the quality of life, bringing more clinical benefits to patients.


[1] Brahmer JR, TYKODI SS, Chow Lq et al. Safety and Activity of Anti-PD-L1 Antibody In Patients with Advanced Cancer [J]. N ENGL J MED, 2012, 366: 2455-2465.

[2] Li J, Deng Y, Zhang W, et al Subcutaneous envafolimab monotherapy in patients with advanced defective mismatch repair / microsatellite instability high solid tumors [J] Journal of Hematology & Oncology, 2021, 14 (1):.. 95.

[3] Papadopoulos KP, HARB W, Peer CJ, ET Al. First-in-Human Phase I Study of Envafolimab, A Novel Subcutaneous Single-Domain Anti-PD-L1 Antibody, In Patients with Advanced Solid Tumors [J]. ONCOLOGIST, 2021

[4] CHEST.2021; S0012-3692 (21) 00340-8.DOI: 10.1016 / j.chest.2021.02.032. Approval number xzxk-2021-278

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