Leads Biolabs wins IND approval for Opamtistomig in metastatic CRC
Nanjing Leads Biolabs has received IND approval from China's Centre for Drug Evaluation for a Phase Ib/II trial of its bispecific antibody Opamtistomig (LBL-024) in metastatic colorectal cancer. The open-label, multicentre study will assess Opamtistomig in combination regimens and explore predictive biomarkers in patients with metastatic colorectal cancer, extending the asset's investigated indications beyond biliary tract cancer, gastric cancer and oesophageal squamous cell carcinoma.
The approval adds a meaningful strategic dimension. Colorectal cancer is one of the largest oncology markets globally, with approximately 1.93 million new cases and 904,000 deaths recorded worldwide in 2022, according to the International Agency for Research on Cancer. In China alone, the disease ranked second in incidence in 2022, with more than 517,000 new diagnoses.
The MSS problem
The scientific rationale for testing an IO 2.0 agent in this setting is well-grounded. Conventional PD-1/PD-L1 checkpoint inhibitors are approved for the microsatellite instability-high subset of metastatic colorectal cancer, but that group represents only around 5% of patients. The remaining 95%, whose tumours are microsatellite stable, are largely resistant to standard immunotherapy. First- and second-line care for these patients continues to rely on chemotherapy combined with targeted agents, leaving substantial unmet need.
Opamtistomig addresses this biology by simultaneously blocking PD-L1-mediated immune suppression and conditionally activating the 4-1BB co-stimulatory receptor. The dual mechanism is designed to reactivate exhausted T cells and drive sustained proliferation, a profile that Leads Biolabs argues could convert immunologically cold tumours into ones that respond to immune intervention.
Charles Cai, chief medical officer at Leads Biolabs, said: "MSS/pMMR mCRC is widely recognised as an immunologically 'cold' tumour, and patients continue to face significant unmet medical needs with limited effective treatment options. Through the synergistic dual targeting of PD-L1 and 4-1BB, Opamtistomig has the potential to restore anti-tumour immune activity in cold tumours, a differentiated mechanism that has already shown encouraging preliminary signals in earlier clinical studies."
Competitive landscape
The broader 4-1BB agonist field has historically been complicated by liver toxicity, an issue that plagued early monospecific 4-1BB agonists from larger players. Bispecific formats that conditionally activate 4-1BB only in the tumour microenvironment have emerged as the preferred engineering approach to avoid systemic toxicity, and Leads Biolabs is among a cohort of companies pursuing this strategy. The company reports that Opamtistomig carries a safety profile comparable to standard PD-1/PD-L1 inhibitors, a claim the ongoing and future trials will need to substantiate in larger cohorts.
Opamtistomig has received Breakthrough Therapy Designation from China's NMPA, as well as FDA Fast Track Designation and Orphan Drug Designation for extrapulmonary neuroendocrine carcinoma, and an Orphan Drug Designation from the European Commission for the same indication. It is the first 4-1BB-targeting bispecific to enter a single-arm pivotal trial as monotherapy, according to the company. Those regulatory recognitions in neuroendocrine carcinoma reflect genuine clinical momentum, though translating signals across tumour types, particularly into immunologically cold MSS colorectal cancer, remains a high bar. Near-term milestones will include safety and preliminary efficacy readouts from the newly approved Phase Ib/II cohorts, as well as data updates from the existing registrational programme in EP-NEC.