GV20 Therapeutics' Novel First-in-Class IGSF8-Targeting Antibody GV20-0251 Receives IND Approval in China for Advanced Solid Tumors

Screenshot source: CDE official website

Immune checkpoint blockade (ICB) is a revolutionary cancer treatment method with inspiring clinical outcomes. However, ICB therapy benefits only a small number of cancer patients, and a large number of patients still respond poorly to existing immunotherapies. Therefore, how to suppress tumor immune escape and identify new targets for immunotherapy remains a critical issue of global concern in the field of cancer treatment.

According to research, most tumors existMHCⅠ Antigen Presentation DefectAnd can lead to tumor resistance to existing ICB drugs.In theory, the natural killer (NK) cells of the innate immune system in the body specifically identify and attack cells with antigen presentation defects and under stress. So why are cancer cells with antigen presentation defects not killed by NK cells?

On April 23, 2024, GV20 TherapeuticsCellThe article titled "IGSF8 is an innate immune checkpoint and cancer immunotherapy target" was published in the journal. The study found that IGSF8, a member of the EWI subfamily within the immunoglobulin superfamily, plays a critical role.IGSF8 Can Inhibit the Tumor-Killing Ability of NK Cells by Binding to MHC-I Receptors on NK Cells。Knocking out IGSF8 can not only restore the cytotoxicity of NK cells but also inhibit tumor growth, making it a potential novel immunotherapy target.

According to a previous press release from GV20 Therapeutics, the company's team de novo designed an antibody with high affinity for both human and mouse IGSF8. This antibody not only blocks the interaction between IGSF8 and NK receptors KIR3DL2 and Klra9, but also enhances the killing of various types of cancer cells by NK cells. Moreover, its combination with PD1 antibody shows significant synergistic effects. This IGSF8 monoclonal antibody is the GV20-0251 injection that has been approved for clinical trials.

According toClinicalTrialsAccording to the official website, GV20 Therapeutics is currently conducting a Phase 1/2 clinical study in the United States. This study aims to evaluate the preliminary efficacy and safety of GV20-0251 injection as a monotherapy and in combination with the anti-PD-1 monoclonal antibody pembrolizumab for the treatment of advanced solid tumors.

In September 2024, researchers presented the preliminary results of this Phase 1/2 study at the ESMO conference. As of July 1, 2024, 38 patients were enrolled across six dose levels (0.5, 1, 3, 6, 10, and 20 mg/kg) and two regimens (Regimen A D1/D8 Q3W, Regimen C D1 Q3W). The median age of the enrolled patients was 62 years, with a median of four prior treatment lines. The results showed,GV20-0251 was well-tolerated at all doses without dose-limiting toxicity.In patients with metastatic cutaneous melanoma, two partial responses (one confirmed and the other unconfirmed) were observed when treated at 3 mg/kg (Regimen A) and 10 mg/kg (Regimen C), respectively. Among 29 evaluable patients, 14 had stable disease, including four with tumor shrinkage. The researchers believed that GV20-0251, a potential "first-in-class" antibody targeting the immune checkpoint IGSF8 in tumors, was safe and well-tolerated at doses up to 20 mg/kg in heavily pretreated patients with advanced solid tumors and demonstrated preliminary clinical activity.

This timeGV20-0251 Injection Approved for Clinical Trials in China, Signaling the Upcoming Clinical Research in the Country.