The world's first subcutaneous injection of PD-L1 drug is here!

*Only for medical professionals to read for reference.
Chinese immunotherapy adds another weapon! On November 25, 2021, the National Medical Products Administration (NMPA) of China approved the PD-L1 inhibitor envolimab (envafolimab) for unresectable or metastatic use through the priority review and approval procedure Treatment of adult patients with advanced solid tumors with highly unstable microsatellites (MSI-H) or mismatch repair gene defects (dMMR), including advanced disease progression after previous treatment with fluorouracil, oxaliplatin, and irinotecan Patients with colorectal cancer and other patients with advanced solid tumors who have progressed after previous treatment and have no satisfactory alternative treatment options
.

The drug is the original PD-L1 monoclonal antibody in China, and it has a unique subcutaneous injection administration method in the world.
Compared with other similar products currently on the market, it has obvious advantages.
Its convenient administration method and good efficacy and safety are Chinese cancer patients bring a new edge in immunotherapy, so the approval of this listing is of great significance
.

(NMPA) Screenshot This approval is based on the significant benefits shown in the Phase II registered clinical study of Envolimab for the treatment of MSI-H/dMMR solid tumor patients.
As an innovative drug, Envolimab is in II Shortly after the release of the data of the first phase of the study, it was quickly included in the priority review and was approved recently, officially entering the field of advanced solid tumors in China’s MSI-H/dMMR, bringing new treatment options and survival hopes to patients, and also leading Chinese tumors Immunotherapy is moving further towards the era of precision treatment
.

Focusing on MSI-H/dMMR, Envolimab fully demonstrates the value of immunotherapy MSI-H/dMMR is currently one of the most important biomarkers for predicting the efficacy of immunotherapy, and has been applied to gastric cancer and colorectal cancer.
Screening of a variety of advanced solid tumor immunotherapy advantage populations
.

The latest 2021 V1 National Comprehensive Cancer Network (NCCN) Gastric Cancer Guidelines have raised the recommended level of MSI/MMR testing.
It is recommended that all newly diagnosed gastric cancer patients should undergo MSI polymerase chain reaction (PCR) testing or mismatch repair protein (MMR) ) Immunohistochemistry (IHC) test [1]
.

The approval of Envolimab is based on the results of a domestic phase II clinical study.
Envolimab as a single agent (administered at 150mg QW) is used to treat 103 patients with MSI-H/dMMR solid tumors as a second-line or higher treatment objective.
The response rate (ORR) was 42.
7%, including 65 patients with colorectal cancer, and the ORR reached 43.
1%
.

The median progression-free survival (PFS) was 11.
1 months, and the 1-year overall survival (OS) rate was 74.
6% [2]
.

The results of this study prove that Envolimab has a good therapeutic value in patients with advanced solid tumors of MSI-H/dMMR
.

Table 1 The curative effect of envolimab in the treatment of Chinese patients with MSI-H/dMMR solid tumors and the first phase I clinical trial of envolimab in humans [3] explored a more convenient mode of medication, and proceeded on the original basis For dose exploration, 10 subjects were injected with 300 mg of envolimab subcutaneously, once every 4 weeks (Q4W)
.

After the first administration, the half-life of the drug is about 15 days, and after 5 cycles of administration, the steady-state half-life of the drug is 23 days
.

In addition, the peak plasma concentration and the area under the curve of envolimab in humans are not affected by the injection site.
The simulation results of pharmacokinetics support it.
The subsequent fixed dose of 300 mg Q3W or 400 mg Q4W can be given.
The medication plan greatly improves the convenience of medication
.

The world’s first subcutaneous injection of PD-L1 monoclonal antibody to help achieve chronic disease management.
Unlike other immune checkpoint inhibitors, envolimab is the world’s first subcutaneous PD-L1 inhibitor, which is taken subcutaneously.
The injection method of administration is relatively stable at room temperature, and the injection site is less restricted, and the administration can be completed easily
.

The PD-1/PD-L1 inhibitors currently on the market need to be observed for infusion reactions after intravenous injection, so it takes longer
.

Envolimab breaks the previous administration mode of intravenous infusion of PD-1/PD-L1 inhibitors.
The subcutaneous administration method avoids the appearance of infusion reactions and greatly shortens the administration time, whether it is Both the follow-up of patients and the management of medical resources have shown their unique advantages
.

Subcutaneous injection not only brings the possibility that patients can take medicines in the nearest hospital or even at home, but also significantly reduces the burden of medical travel and related expenses, and it also reduces the intravenous administration of PD-1/PD-L1 monoclonal antibody.
Risk of adverse reactions
.

For elderly cancer patients and cancer patients with poor physical fitness scores, while pursuing curative effects, there is an urgent need for immune drugs that can take into account safety, tolerability and convenience
.

Envolimab is very suitable for patients who cannot take intravenous injections, which can improve the compliance of patients with medication and improve the quality of life of patients
.

The current exploration of extending the interval between envolimab administrations has further increased the convenience of envolimab
.

Envolimab's unique advantages in drug delivery are of milestone significance for the long-term management of tumors as chronic diseases
.

Envolimab has a controllable safety and escorts patients' medication.
Envolimab has good tolerability and safety.
The safety data of the domestic phase II clinical study of Envolimab shows [2], Among 103 patients with MSI-H/dMMR solid tumors, 16 patients (15.
5%) had grade 3-4 drug-related adverse events during treatment (TEAE), and there was no study drug-related grade 5 TEAE
.

In addition, it is worth noting that in the study, the incidence of immune pneumonia was 0% and the incidence of colorectitis was 0%
.

At the same time, envolimab is administered by subcutaneous injection, and the incidence of infusion adverse reactions is 0%; the incidence of partial injection reactions is only 8.
7%, all of which are grade 1-2.
There are no related serious adverse events or permanent drug withdrawal.
Time happened
.

Table 2 The safety of envolimab in the treatment of Chinese patients with MSI-H/dMMR solid tumors.
Immune-related pneumonia and enteritis are one of the possible adverse events (AE) in the clinical use of other PD-1/PD-L1 monoclonal antibodies Although it is not common, it is a fatal threat.
Because patients with non-small cell lung cancer (NSCLC) often receive immunotherapy, many evidences of immune pneumonia have been found in the real world.
Analysis of lung cancer cases (NSCLC accounted for 93.
7%, 61.
7% of which were adenocarcinoma and 28.
5% of squamous cell carcinoma) treated with three listed PD-1/CTLA-4 inhibitors in 6 medical centers in Nazhou [4], the results showed In 17.
5% of cases, immunotherapy drugs were discontinued due to irAE
.

About 10% of patients develop immune pneumonia during treatment, and the median time to onset is 52 days after diagnosis
.

For more severe immune pneumonia, clinical treatment is difficult, and immunotherapy is usually stopped and hormone control is used.
This not only affects the patient's anti-tumor treatment, but also increases the additional costs incurred in the treatment of AEs
.

The listing of Envolimab will effectively avoid the occurrence of related adverse reactions
.

It can be seen from the phase II study that Envolimab injection not only exhibits long-lasting anti-tumor activity and superior convenience in patients with MSI-H/dMMR solid tumors, but also shows its controllable Security
.

A new immunotherapy weapon, envolimab brings multiple benefits to patients.
With the advent of the era of precision tumor immunotherapy, the role of MSI-H/dMMR as a predictor of tumor immunotherapy efficacy has become increasingly prominent and has become the focus of clinical attention
.

Envolimab injection is the world's first subcutaneous injection of PD-L1 inhibitor.
Clinical research data confirms that it has good anti-tumor efficacy and controllable safety for advanced solid tumors of MSI-H/dMMR in China.
MSI-H/dMMR advanced solid tumor patients who have failed at least the first-line standard treatment in the past bring new treatment options and hope for more MSI-H/dMMR patients
.

Therefore, Envolimab is expected to lead the immunotherapy into the era of precision medication.
After it is approved for marketing and enters clinical application in China, as domestic clinics continue to accumulate experience in the use of subcutaneous immunotherapy drugs, it may bring more in the future New exploration directions, such as research on combined treatment of multiple drugs based on their good safety, exploration of drug delivery cycles, and optimization of the entire treatment management of patients, etc.
, will enrich the new opportunities brought by immunotherapy
.

It is expected that the launch of Envolimab injection will have a place in the future development of immunotherapy, improve the quality of life of patients, and bring more clinical benefits to patients
.

References: [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].
The Oncologist , 2021[4]Chest.
2021;S0012-3692(21)00340-8.
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Approval number XZXK-2021-278*This article is only used to provide scientific information to medical professionals , Does not represent the views of this platform