On June 19, the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) announced that Livzon Pharmaceutical’s LM-108 injection has been proposed for inclusion in the breakthrough therapy designation. The combination of Kefeqibai monoclonal antibody injection (LM-108) with toripalimab is being considered for the treatment of patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma who are CCR8-positive and have failed prior first-line standard therapy.
LM-108 is a novel Fc-optimized, anti-CCR8 monoclonal antibody that selectively depletes tumor-infiltrating Tregs.
About CCR8:
CCR8 (chemokine receptor 8) is a member of the chemokine receptor subfamily under the G protein-coupled receptor (GPCR) family. Previous studies revealed that the expression of CCR8 is low in peripheral blood cells and normal tissues, but is specifically upregulated in tumor-infiltrating Tregs in multiple cancers including breast cancer, colorectal cancer, and lung cancer. Anit-CCR8 antibodies can selectively mediate the depletion of tumor-infiltrating Tregs, thereby enhancing the anti-tumor immune response and inhibiting tumor growth.
At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, a pooled analysis of three Phase 1/2 studies on the combination of LM-108 and anti-PD-1 therapy in gastric cancer patients was presented.
Methods: Eligible patients with gastric cancer treated with LM-108 in combination with an anti-PD-1 antibody were included in the analysis. Patients received intravenous LM-108 at dose levels of 3 mg/kg Q2W, 6 mg/kg Q3W, or 10 mg/kg Q3W plus an anti-PD-1 antibody (intravenous pembrolizumab 200 mg Q3W or 400 mg Q6W or toripalimab 240 mg Q3W). The primary endpoint was investigator-assessed ORR per RECIST v1.1. The secondary endpoints included safety, other efficacy outcomes, and biomarkers analysis. Data cutoff date for the pooled analysis was December 25, 2023.
Results: Forty-eight patients with gastric cancer (median age: 60.5 years; male: 72.9%) from China, USA, and Australia were treated ≥ 1 dose of LM-108 in combination with pembrolizumab or toripalimab. Most (n = 47, 97.9%) patients had received at least 1 prior anticancer treatment, and 43 (89.6%) had received prior anti-PD-1 therapy. Treatment-related adverse events (TRAEs) occurred in 39 (81.3%) patients, in which the most common events (≥15%) were alanine transaminase increased (25.0%), aspartate transaminase increased (22.9%), white blood cell decreased (22.9%), anemia (16.7%). Grade ≥ 3 TRAEs occurred in 18 (37.5%) patients, the most common events (≥ 4%) were anemia (8.3%), lipase increased (4.2%), rash (4.2%), and lymphocyte count decreased (4.2%). Among 36 efficacy-evaluable patients across all regimens, ORR was 36.1% and DCR was 72.2% . The median PFS was 6.53 months. Among 11 patients whose disease had progressed on first-line treatment, ORR was 63.6% and DCR was 81.8%. Of the 11 patients who progressed on first-line treatment, 8 had high CCR8 expression. Among these 8 patients, ORR was 87.5% and DCR was 100%, with 1 CR, 6 PR, and 1 SD observed.
Conclusions: LM-108 in combination with an anti-PD-1 antibody showed promising antitumor activity in patients with gastric cancer that was resistance to anti-PD-1 therapy. The combination therapy was well tolerated.
At present, there are still many clinical trials of new anti-cancer technologies in China seeking patients. Consultation on new drugs and technologies, you can contact Beijing South Region Oncology Hospital International Department.
Phone Number：4008803716
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Post time: Jun-24-2025