Leads Biolabs’ Opamtistomig NDA Accepted in China, Setting Up Potential World-First 4-1BB Therapy
Nanjing Leads Biolabs announced that China’s Center for Drug Evaluation (CDE) under the National Medical Products Administration (NMPA) has formally accepted the New Drug Application (NDA) for Opamtistomig (LBL-024), the company’s internally developed PD-L1/4-1BB bispecific antibody, as monotherapy for patients with previously treated advanced extrapulmonary neuroendocrine carcinoma (EP-NEC). (PR Newswire)
According to Leads Biolabs, Opamtistomig is the first PD-L1/4-1BB bispecific antibody globally to reach the NDA review stage. The drug had already been granted Priority Review by the CDE on July 10, 2026, accelerating its path toward a potential commercial approval. (PR Newswire)
If approved, Opamtistomig would become the world’s first approved antibody drug directly targeting 4-1BB and the first approved agonistic antibody, according to the company. It would also establish 4-1BB as the fourth major immuno-oncology target to have an approved therapy, following PD-1/PD-L1, CTLA-4 and LAG-3. (PR Newswire)
Targeting a Difficult-to-Treat Neuroendocrine Cancer
EP-NEC is a rare and highly aggressive malignancy arising outside the lungs. Patients with advanced disease have limited treatment options, particularly after progression on multiple lines of systemic therapy.
The current application covers Opamtistomig as a single-agent treatment for previously treated advanced EP-NEC. Leads Biolabs previously described the pivotal population as patients whose disease had progressed after two or more prior lines of systemic therapy, an area where existing later-line therapies provide limited clinical benefit. (PR Newswire)
The NDA is supported by a registrational clinical study led by Professor Shen Lin of Peking University Cancer Hospital and conducted at 34 clinical sites. The study enrolled 96 patients with EP-NEC, with enrollment completed in August 2025. Leads Biolabs said detailed data from the study are expected to be presented at a leading international medical congress. (PR Newswire)
The regulatory filing therefore represents one of the most advanced attempts yet to turn 4-1BB agonism—a mechanism that has challenged drug developers for years—into an approved cancer therapy.
Opamtistomig Combines PD-L1 Blockade With 4-1BB Activation
Opamtistomig was developed using Leads Biolabs’ proprietary X-Body bispecific antibody platform and is designed to attack tumor immune evasion through two complementary mechanisms.
On one side, the molecule targets PD-L1, blocking PD-1/PD-L1-mediated immunosuppressive signaling and effectively releasing a key immune “brake” on T cells.
On the other side, Opamtistomig is designed to conditionally activate the 4-1BB co-stimulatory pathway, providing an immune “accelerator” that can enhance T-cell activation, proliferation and anti-tumor activity.
The combination is intended to concentrate 4-1BB activation within the tumor microenvironment, generating stronger anti-tumor immunity while reducing the systemic activation that contributed to toxicity problems with earlier generations of 4-1BB agonists. (LeadsBioLabs)
In simple terms, the strategy combines removing the brake through PD-L1 blockade with pressing the accelerator through 4-1BB activation.
That dual mechanism could be particularly relevant in tumors that respond poorly to conventional checkpoint inhibitors or have developed resistance to PD-1/PD-L1 therapy.
Reviving the Long-Pursued 4-1BB Target
4-1BB, also known as CD137, has long attracted interest as an immuno-oncology target because activating the receptor can stimulate T-cell proliferation and strengthen anti-tumor immune responses.
However, translating that biology into successful drugs has proven difficult.
Earlier 4-1BB agonist antibodies encountered a challenging efficacy-safety tradeoff. Urelumab, for example, demonstrated significant liver toxicity at higher doses, while the better-tolerated utomilumab showed relatively limited anti-tumor activity. As a result, despite years of development efforts, no 4-1BB-targeting therapy has yet reached the market. (HKEXnews)
Bispecific antibodies such as Opamtistomig attempt to solve this problem by making 4-1BB activation dependent on engagement with another target—in this case PD-L1—thereby concentrating co-stimulatory activity within tumors rather than activating 4-1BB broadly throughout the body.
Leads Biolabs says its X-Body platform is specifically designed to facilitate 4-1BB receptor activation when the molecule binds its tumor-associated target, potentially increasing anti-tumor immune activity while mitigating systemic toxicity. (LeadsBioLabs)
Earlier Clinical Data Provided Proof of Concept
Earlier Phase I/II clinical results have already provided evidence supporting Opamtistomig’s mechanism.
In a first-in-human Phase I/II study reported at the 2024 American Society of Clinical Oncology annual meeting, investigators evaluated LBL-024 across seven dose levels ranging from 0.2 mg/kg to 25 mg/kg, administered intravenously every three weeks. No dose-limiting toxicity was observed during dose escalation and the maximum tolerated dose was not reached. A 15 mg/kg dose was selected for Phase II development. (ASCO Publications)
As of the October 31, 2023 data cutoff, 162 patients had been enrolled across the Phase I and Phase II portions. Among them, 77.8% experienced treatment-related adverse events of any grade and 21.0% experienced Grade 3 or higher treatment-related adverse events. Investigators also reported encouraging anti-tumor activity, particularly among patients with EP-NEC. (ASCO Publications)
Those early signals helped propel Opamtistomig into registrational development.
Leads Biolabs now describes the candidate as having a safety profile comparable to PD-1/PD-L1 inhibitors while potentially providing broader anti-tumor activity. The company is exploring the molecule across numerous solid tumors, although these broader efficacy claims will ultimately need to be established through mature clinical datasets and confirmatory studies. (PR Newswire)
Regulatory Momentum Extends Beyond China
Opamtistomig has also accumulated several expedited regulatory designations outside China.
The program received Breakthrough Therapy Designation from China’s NMPA in October 2024 and Orphan Drug Designation from the U.S. FDA for neuroendocrine carcinoma in November 2024. In January 2026, the FDA granted Fast Track Designation for EP-NEC, while the program also received orphan designation in Europe. (PR Newswire)
The CDE subsequently placed the application into its Priority Review and Approval procedure on July 10. Under China’s applicable regulatory framework, the priority-review pathway has a target review period of approximately 130 working days, compared with 200 working days for ordinary review, potentially shortening the route to commercialization. (BioPharm International)
Potential Beyond EP-NEC
EP-NEC could ultimately represent only the first indication for Opamtistomig.
Leads Biolabs is developing the antibody across a broad range of solid tumors. The company says Opamtistomig has been evaluated across 13 solid-tumor indications in China, including programs in non-small cell lung cancer, small cell lung cancer, biliary tract cancer, ovarian cancer, esophageal squamous cell carcinoma, hepatocellular carcinoma, gastric cancer, triple-negative breast cancer and melanoma. (PR Newswire)
The broader strategy is to position Opamtistomig as a potential next-generation immunotherapy backbone, particularly for tumors that are resistant or poorly responsive to existing checkpoint inhibitors.
That ambition remains to be demonstrated in larger controlled studies. Nevertheless, an approval in EP-NEC would provide an important clinical validation of the PD-L1/4-1BB bispecific approach and could revive broader interest in 4-1BB as an immuno-oncology target.
A Potential Milestone for 4-1BB Drug Development
The acceptance of the Opamtistomig NDA moves Leads Biolabs considerably closer to what could be a landmark approval.
After years in which 4-1BB agonists struggled to balance immune activation against toxicity, Opamtistomig’s tumor-localized bispecific design offers a different approach: combine checkpoint blockade and co-stimulation within a single molecule while restricting strong 4-1BB activation primarily to the tumor microenvironment.
If the NMPA ultimately approves the therapy, Opamtistomig could become not only Leads Biolabs’ first major commercial product but also a significant proof of concept for a new generation of conditional immune agonists.
Attention will now turn to the forthcoming presentation of the 96-patient registrational EP-NEC dataset, which should provide a much clearer picture of the magnitude and durability of clinical benefit behind the NDA—and potentially determine how broadly the Opamtistomig platform could compete in the next generation of cancer immunotherapy.
References
- Leads Biolabs — Opamtistomig NDA Acceptance Announcement, August 21, 2026.
Leads Biolabs / PR Newswire announcement - Leads Biolabs — Priority Review Granted to Opamtistomig, July 10, 2026.
Priority Review announcement - Leads Biolabs — X-Body Bispecific Antibody Platform.
X-Body technology platform - Journal of Clinical Oncology — Phase I/II study of LBL-024 in advanced malignant tumors and neuroendocrine carcinoma.
JCO / ASCO abstract 4010 - Hong Kong Stock Exchange — Leads Biolabs regulatory filing/prospectus discussing 4-1BB drug development and Opamtistomig.
HKEX filing - BioPharm International — Opamtistomig enters China Priority Review for advanced EP-NEC.
BioPharm International coverage
