China's Center for Drug Evaluation (CDE), part of the National Medical Products Administration (NMPA), has approved an investigational new drug (IND) application for an open-label, multicenter phase Ib/II trial evaluating Nanjing Leads Biolabs' opamtistomig (LBL-024) in combination regimens for metastatic colorectal cancer (mCRC).¹ The trial will assess safety and efficacy while exploring predictive biomarkers for response.¹ The approval extends opamtistomig's immuno-oncology footprint from biliary tract cancer, gastric cancer, and esophageal squamous cell carcinoma into colorectal cancer, an indication the company describes as an area of high unmet clinical need.¹
How does opamtistomig work?
“Through the synergistic dual targeting of PD-L1 and 4-1BB, opamtistomig has the potential to restore anti-tumor immune activity in cold tumors, a differentiated mechanism that has already shown encouraging preliminary signals in earlier clinical studies.”
—Dr. Charles Cai, chief medical officer of Leads Biolabs
Opamtistomig is a bispecific antibody built on Leads Biolabs' proprietary X-Body platform that simultaneously targets PD-L1 and the co-stimulatory receptor 4-1BB.¹ The molecule is designed to block PD-1/PD-L1-mediated immune suppression while conditionally activating 4-1BB, an agonist pathway associated with reactivating exhausted T cells.¹ The company states this dual mechanism produces a synergistic anti-tumor immune response, with a safety profile comparable to existing PD-1/PD-L1 inhibitors alone.¹
Why does colorectal cancer need a new immunotherapy approach?
The majority of metastatic colorectal cancer, roughly 95% of cases, is microsatellite stable (MSS) or mismatch repair-proficient (pMMR), and these tumors are intrinsically resistant to checkpoint inhibitor monotherapy.² Low tumor mutational burden, minimal T-cell infiltration, and an immunosuppressive tumor microenvironment are among the mechanisms cited for this resistance.² According to 2022 data from the International Agency for Research on Cancer cited in the release, colorectal cancer accounted for approximately 1.926 million new cases and 904,000 deaths globally that year, making it one of the most common gastrointestinal malignancies worldwide.¹