Givastomig Demonstrates Anti-Tumor Activity in Gastric Cancer via Targeted T-Cell Activation
Key Insights
I-Mab (search)'s givastomig, a Claudin18.2 (search) x 4-1BB (search) bispecific antibody, shows promising anti-tumor activity by selectively activating T cells within CLDN18.2-expressing tumors.
Preclinical studies reveal givastomig's ability to induce localized immune activation, increasing CD8+/Treg cell ratio and eliciting a lasting memory response against tumor rechallenge.
The bispecific antibody binds to tumor cells across varying CLDN18.2 expression levels, activating 4-1BB (search) only in the presence of CLDN18.2, reducing potential systemic toxicity.
I-Mab (search)'s bispecific antibody, givastomig, has demonstrated significant anti-tumor activity in preclinical models of gastric cancer (search) by selectively activating T cells within tumors expressing Claudin18.2 (search) (CLDN18.2). The findings, published in the Journal for Immuno-Therapy of Cancer (JITC), highlight givastomig's potential as a targeted immunotherapy for gastric cancer, a disease with limited treatment options and poor prognosis.
Givastomig, also known as TJ-CD4B/ABL111, is engineered to bind to CLDN18.2-expressing cancer cells and the co-stimulatory receptor 4-1BB (search) on adjacent T cells. This dual-targeting mechanism aims to activate T cells specifically within the tumor microenvironment, triggering a potent tumor-killing effect while minimizing systemic toxicity.
Preclinical Efficacy and Safety
Preclinical studies demonstrated that givastomig effectively binds to tumor cells with varying levels of CLDN18.2 expression and activates 4-1BB (search) signaling only in the presence of CLDN18.2, indicating a targeted effect. In vivo studies using CLDN18.2-expressing tumor models showed that givastomig induced localized immune activation within tumors, increasing the ratio of CD8+ cytotoxic T cells to regulatory T cells (Tregs). This resulted in superior anti-tumor activity and a long-lasting memory response against tumor rechallenge.
Dr. Lin Shen, Professor of Clinical Oncology at the Beijing Cancer Hospital of Peking University, noted, "The findings from our research demonstrate the significant potential of givastomig in treating gastric cancer (search) patients with varying levels of CLDN18.2 expression. By activating 4-1BB (search) signaling in a CLDN18.2 engagement-dependent manner, givastomig can avoid the risk of liver toxicity and systemic immune response commonly observed with other 4-1BB stimulating agents in previous clinical trials."
Clinical Development and Future Outlook
Givastomig is currently undergoing Phase 1 clinical studies in both the U.S. and China. Preliminary data from these studies have shown a favorable safety profile and promising efficacy signals. I-Mab (search) intends to present additional clinical data from the ongoing study at a major medical conference in the second half of the year.
Dr. Andrew Zhu, President of I-Mab (search), stated, "This molecule has demonstrated promising results in this study by effectively activating T cells and triggering a localized immune response within the tumor microenvironment. With ongoing clinical studies, we aim to build upon these findings and ultimately make this innovative therapy accessible to patients with gastric cancer (search)."
The U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for givastomig for the treatment of gastric cancer (search), including cancer of the gastroesophageal junction, in March 2022.