Urelumab

Nanjing Leads Biolabs (HK: 9887.HK) has received approval from China’s National Medical Products Administration to initiate a pivotal Phase III trial of opamtistomig (LBL-024) in the first-line treatment of advanced extrapulmonary neuroendocrine carcinoma (EP-NEC). Opamtistomig is a PD-L1/4-1BB-targeted bispecific antibody (BsAb). Leads Biolabs appears to be the only company currently advancing a pivotal program specifically in EP-NEC, a rare and aggressive malignancy for which no drug has ever received regulatory approval in any jurisdiction. EP-NEC is a heterogeneous group of poorly differentiated neuroendocrine tumors arising outside the lung. Clinically, it is treated by analogy to extensive-stage small cell lung cancer, with platinum-based chemotherapy — typically etoposide combined with cisplatin or carboplatin — serving as the de facto first-line standard. That standard produces an objective response rate of 30% to 50% and a median overall survival of approximately one year. No checkpoint inhibitor, targeted agent, or any other drug carries a label specifically for EP-NEC. The use of Roche’s atezolizumab (Tecentriq) or AstraZeneca’s durvalumab (Imfinzi) in this setting is entirely off-label, extrapolated from SCLC trial data. The immunological profile of EP-NEC compounds the therapeutic challenge. The tumor is generally characterized as immunologically cold, with low baseline T-cell infiltration and limited responsiveness to single-agent PD-1/PD-L1 blockade. That biology has historically made EP-NEC a poor candidate for the checkpoint inhibitor combinations that have reshaped treatment in NSCLC, bladder cancer, and other solid tumors. Mechanism rationale for a PD-L1/4-1BB bispecific antibody in cold tumors Opamtistomig is engineered to address both arms of immune suppression simultaneously. Developed on Leads Biolabs’ proprietary X-Body bispecific platform, the molecule binds PD-L1 to block the PD-1/PD-L1 suppressive axis while conditionally agonizing 4-1BB, a co-stimulatory receptor on T cells and natural killer cells. The conditional design is mechanistically important: 4-1BB agonism is activated only when the antibody bridges PD-L1 on tumor cells and 4-1BB on adjacent immune effector cells simultaneously. This spatial requirement is intended to restrict T-cell activation to the tumor microenvironment, reducing the systemic hepatotoxicity that derailed earlier unconjugated 4-1BB agonists such as urelumab in clinical development. The rationale for deploying this mechanism in EP-NEC rests on the biology of 4-1BB signaling. Agonism of 4-1BB can reactivate exhausted T cells and drive robust T-cell proliferation, effects that are particularly relevant in immunologically cold tumors where PD-L1 blockade alone provides insufficient co-stimulation to generate durable antitumor responses. By coupling checkpoint blockade with co-stimulatory activation in a single molecule, opamtistomig is designed to convert cold tumors into immunologically active ones — a hypothesis that the Phase Ib/II proof-of-concept study in EP-NEC was built to test. Phase Ib/II data The NMPA’s Center for Drug Evaluation cleared the Phase III initiation based on efficacy and safety data from a completed Phase Ib/II study. Leads Biolabs has indicated that full results from that study are planned for presentation at the 2026 ESMO Congress. The company has not disclosed the specific response rate, progression-free survival, or overall survival figures from the Phase Ib/II cohort in this announcement. Without detailed efficacy data, external assessment of the magnitude and durability of benefit remains limited ahead of the planned ESMO 2026 presentation The new Phase III study is a randomized, double-blind, multicenter trial led by Professor Lin Shen of Peking University Cancer Hospital. It evaluates opamtistomig in combination with chemotherapy as a first-line treatment for advanced EP-NEC. The design represents a material step forward from Leads Biolabs’ earlier EP-NEC program: the company had previously received CDE approval for a pivotal single-arm registration trial of opamtistomig as monotherapy in patients with third-line or later EP-NEC. The new Phase III extends the addressable patient population to the first-line setting and introduces a combination strategy, increasing both the potential commercial scope and the regulatory complexity of the development program. Leads Biolabs also stated it plans to submit a biologics license application to the NMPA in Q3 2026 for opamtistomig as a single agent in the 3L+ EP-NEC monotherapy indication, running the BLA process in parallel with the new first-line Phase III. Opamtistomig has accumulated regulatory designations from the NMPA, the US FDA, and the European Commission. China’s NMPA granted Breakthrough Therapy Designation in October 2024 for EP-NEC. The FDA granted Orphan Drug Designation for neuroendocrine carcinoma in November 2024, followed by Fast Track Designation for EP-NEC in January 2026. The European Commission granted Orphan Drug Designation for EP-NEC in the same month. Competitive context for advanced EP-NEC first-line therapy The investigational pipeline for EP-NEC remains early-stage outside of Leads Biolabs. Boehringer Ingelheim’s BI 764532, a DLL3 × CD3 bispecific T-cell engager, is in Phase I/II development for EP-NEC and extensive-stage SCLC, with activity in the post-first-line setting. Zymeworks and Zai Lab’s zocilurtatug pelitecan, a DLL3-targeting antibody-drug conjugate, is also in Phase I/II for later-line EP-NEC. Both programs are earlier in development and focused on different lines of therapy and distinct mechanisms. Neither has entered a pivotal or registrational study in EP-NEC. Opamtistomig’s first-mover position in a pivotal Phase III — combined with a concurrent 3L+ BLA filing plan — gives Leads Biolabs a structural advantage in the race toward the first regulatory approval specifically for this indication. Whether that advantage translates into an approved product will depend on the Phase III data readout and the full Phase Ib/II dataset that ESMO 2026 is expected to provide the first comprehensive look at. 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