Can the PD-(L)1 double antibody surpass the PD-(L)1 monoclonal antibody?

Author: Leaf

On September 24, Kangfang Bio announced that NMPA has officially accepted its PD-1/CTLA4 bispecific antibody Cadonilimab (AK104) for the treatment of recurrent or metastatic cervical cancer, and received priority review

At present, 6 dual-antibody drugs have been approved or applied for marketing in the world.

Dual antibody drugs approved or applied for marketing worldwide

Source: NextPharma

There are many types of PD-(L)-based dual antibody drugs in the choice of combination targets, CTLA4 is only one of them, and the "dual immune checkpoint" combination therapy of PD-1+CTLA4 (such as O+Y) has been approved for marketing And gradually expand the scope of population use in clinical development and application

Since there is no direct head-to-head research data, this article is only based on the existing information data, with 4 representative PD-1/CTLA4, PD-L1/CTLA4, PD-1/LAG-3, PD-1/TGF A brief discussion on the -β project is for reference only

Cervical cancer: Cadonilimab PK Pembrolizumab

Pembrolizumab is currently the only PD-1 antibody approved for cervical cancer

Cadonilimab achieved an objective response rate (ORR) of 47.

In June 2021, Kangfang Biological also announced the randomized, double-blind, placebo-controlled phase III study (CTR20211380) of Cadonilimab for the first-line treatment of recurrent or metastatic cervical cancer (CTR20211380) on the drug clinical trial registration and information disclosure platform, which mainly evaluates Cadonilimab+ platinum The efficacy and safety of chemotherapy ± bevacizumab for recurrent or metastatic cervical cancer

Coincidentally, at the just-concluded ESMO2021 conference, Merck announced the results of the KEYNOTE-826 study of pembrolizumab in the first-line treatment of cervical cancer

Although the Phase III study of Cadonilimab (CTR20211380) is not a head-to-head design with Keytruda, it uses the same control drug and dosing schedule as KEYNOTE-826

Non-small cell lung cancer: KN046 PK PD-1 monoclonal antibody

KN046 is a PD-L1/CTLA-4 bispecific antibody independently developed by Corning Jerry.

Non-small cell lung cancer is one of the areas where PD-(L)1 monoclonal antibodies compete most

The final data of the study is not yet mature.

Diffuse large B-cell lymphoma: Tepolizumab PK Pembrolizumab

Tepolizumab (ZL-1301) is a LAG3/PD1 bispecific antibody drug developed by Macrogenics using DART® platform technology.

As Tepolizumab is still in early clinical research, there is not much clinical data released

Solid tumors: JS201 PK Pembrolizumab

JS201 is a PD-1/TGF-β bifunctional fusion protein independently developed by Junshi Bio based on Teriplizumab, which can effectively block PD-1/PD-L1 and mediate anti-PD-1 single antigen resistance The TGF-β immunosuppressive pathway of the drug improves the immune regulation in the tumor microenvironment, thereby promoting the killing effect of the human immune system on tumor cells, effectively enhancing the immune response, and reducing immune escape and the occurrence of drug resistance

JS201 has just entered clinical research, and there is no effective data released yet

Concluding remarks

The enthusiasm of domestic companies to develop bispecific antibody drugs is high, and more than 30 companies have entered the clinic in the field of PD-(L)1 alone
.
Of course, bispecific antibodies with different targets will also cause differences in indications from PD-1/L1 monoclonal antibodies
.
However, in general, bispecific antibodies in the PD-(L)1 field are more in the early clinical stage, and compared with PD-(L)1 monoclonal antibodies, they have not yet formed a strong competitive advantage and momentum
.

The purpose of drug development is to provide patients with better treatment options
.
The PD-(L)1 bispecific antibody is based on the concept of PD-(L)1 monoclonal antibody.
There is no doubt that the success rate of the drug will be greatly improved; however, when PD-(L)1 becomes the standard treatment Or after the recognized preferred treatment, head-to-head research between double antibodies and monoclonal antibodies is inevitable; on the other hand, based on the concept of PD-(L)1 monoclonal antibodies, double antibody drugs should also be developed with PD-(L)1 monoclonal antibodies.
(L)1 Head-to-head research between monoclonal antibodies, thus proving that advanced design concepts are transformed into clinical benefits, and also a manifestation of their clinical value
.

Of course, whether to conduct head-to-head research also involves many factors, so you should not insist on it
.
However, the history of disease treatment is constantly advancing in the head-to-head research of generations of drugs
.
In the same disease environment, PD-(L)1 bispecific antibodies should also dare to be a "bright sword" to PD-(L)1 monoclonal antibody or combination therapy
.