Henlius LAG-3 + PD-1 combination therapy starts clinical trials
HLX26 is an innovative therapy independently developed by Henlius targeting the extracellular domain of lymphocyte-activation gene 3 (LAG-3) humanized monoclonal antibody is intended to be used in the treatment of solid tumors and lymphoma .
LAG-3 is mainly expressed on activated T cells and some NK cells , and plays a negative regulatory role in cell proliferation, activation and homeostasis of T cells. Inhibiting LAG-3 can reactivate T cells and restore their ability to kill tumor cells.
HLX26 blocks the interaction between LAG-3 and its ligands, thereby blocking the LAG-3-mediated signaling pathway that inhibits T cell function, and restores the release of cytokines such as T cells IL-2 and IFN-γ. , by combining it with the recombinant anti-PD-1 monoclonal antibody injection HLX10, it blocks immune escape in the tumor microenvironment to achieve the purpose of inhibiting tumors.
Preclinical pharmacology research, pharmacokinetics research and safety evaluation have proven that HLX26 has anti-tumor effects in vivo and in vitro, and is well tolerated and safe. At the same time, HLX26 showed more significant anti-tumor activity in combination with the recombinant anti-PD-1 humanized monoclonal antibody injection HLX10, with a synergistic effect.
Previously, Henlius had initiated a Phase I clinical study in August 2021 to evaluate the safety and tolerability of HLX26 in patients with advanced/metastatic solid tumors or lymphomas (Registration Number: CTR20211972).
HLX26 Domestic R&D Progress Gantt Chart
From: Insight Database
This study is to evaluate the safety, tolerability, and drug efficacy of HLX26 monoclonal antibody injection combined with PD-1 monoclonal antibody in patients with advanced/metastatic solid tumors. Phase I clinical study on pharmacokinetic characteristics and preliminary effectiveness (registration number: CTR20221603). The primary endpoints were dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) within 3 weeks of the first dose of HLX26 in combination with HLX10.
CTR20221603 Clinical trial
comes from: Insight database
LAG-3 Competition is fierce, with 50 antibody projects around the world under development
LAG-3 is the third commercialized immune checkpoint in the world after PD-1 and CTLA-4. It is already in Excellent efficacy in PD-1 combination therapy.
In March this year, Bristol-Myers Squibb First-in-class dual immunotherapy Relatlimab + Nivolumab fixed-dose combination Opdualag received accelerated approval from the FDA for the treatment of metastatic melanoma. In addition to the standard treatment regimen O+Y combination, It provides new treatment options for patients with melanoma ; BMS has also been extensively developed for other solid tumors.
Compared with CTLA-4, LAG3 has potential advantages in security. In Opdualag's pivotal clinical study, RELATIVITY-047, the 12-month PFS data for the LAG3 combination was similar to the O+Y combination, while the incidence of serious side effects was only 19%, which was much lower than the 59% for the O+Y combination. However, the clinical data of LAG3 combination therapy is relatively less mature than the O+Y regimen, so longer-term data are still needed to show the ultimate benefit to patients.
According to global new drug data from the Insight database, there are currently 50 LAG-3 antibody drug projects under development, 27 of which have entered the clinical development stage, including 18 monoclonal antibodies, 7 double antibodies, and 2 monoclonal antibody combinations. Depending on where they bind LAG3, these antibodies may have different abilities to block the interaction of LAG3 and its various ligands.
Clinical stage LAG3 antibody drug category distribution
From: Insight database
At present, LAG3 antibodies are mainly developed in the form of PD-1 combination. There are two super blockbusters, K drug and O drug. Merck & Co. and Bristol-Myers Squibb. Bristol-Myers Squibb continues to be at the forefront by taking advantage of its first-mover advantage in the immunotherapy field.BMS took the lead in obtaining the first approval, and Merck's MK-4280A has also launched Phase III clinical trials for the first time in September 2021 for PD-L1-positive colorectal cancer. Regeneron/ Sanofi ’s fianlimab is in third place, and Phase III clinical trials for melanoma were also launched on April 6.
has set its sights on China. According to the Insight database, Chinese companies have participated in the development of 20 LAG-3 antibody drugs, 12 of which are monoclonal antibodies. The progress stages are as follows. Among the companies that have submitted PD-(L)1 monoclonal antibodies for approval, Hengrui, , Innovent, BeiGene, Henlius, Yuheng, Kelun... all have LAG-3 monoclonal antibody projects under development . Previously, on May 18, Zhengda Tianqing also joined the competition by introducing LAG3 monoclonal antibody.
Distribution of LAG3 monoclonal antibody R&D status of Chinese companies
From: Insight database
Judging from the trend, LAG3 target project applications have exploded since 2019 and will reach a small peak in 2021. Currently, a total of 15 projects have entered the clinical development stage, including 10 domestic and 5 imported.
Domestic LAG3 project research and development trends
From: Insight database
Innovent Bio is the only company that has both monoclonal antibodies and dual antibodies entering clinical trials. The LAG3 monoclonal antibody IBI110 has started Phase II clinical trials, and the PD-L1/LAG3 dual antibody IBI323 is in the process of clinical trials. Phase I clinical stage. Projects entering Phase II clinical trials also include three LAG3 monoclonal antibodies: SHR-1802 from Hengrui Pharmaceuticals, LBL-007 from BeiGene/Velizhibo, and DNV3 from Shimai Pharmaceuticals.
LAG3 monoclonal antibody in phase II clinical trials in China
From: Insight database
As of today, among the major immune checkpoints after PD-(L)1, TIGIT is the most popular, followed closely by LAG3, both of which are early stage There are many stage projects in reserve and they are ready to go. LAG3 monoclonal antibody was successfully approved for marketing, while TIGIT suffered two setbacks in succession. Will the popularity of the track change in the future? Time will tell.
comes from: Insight database
This article comes from Insight database
