Leads Biolabs' PD-L1/4-1BB Bispecific Opamtistomig Delivers 71% ORR in First-Line NSCLC at WCLC 2026
核心洞察
Updated Phase II data for opamtistomig (搜索) plus chemotherapy in first-line NSCLC showed a 71.0% objective response rate and 95.2% disease control rate among 62 efficacy-evaluable patients.
In squamous NSCLC (搜索), the combination achieved an 87.1% ORR and 86.7% six-month PFS rate, with comparable benefit regardless of PD-L1 (搜索) expression status.
PD-L1 (搜索)-positive non-squamous patients achieved an 81.8% ORR, 100% DCR and 90.0% six-month PFS rate, with responses also seen at low PD-L1 expression.
Nanjing Leads Biolabs (搜索) Co., Ltd. (9887.HK) reported updated Phase II data showing that its proprietary PD-L1 (搜索)/4-1BB (搜索) bispecific antibody opamtistomig (搜索) (LBL-024) combined with chemotherapy produced robust and durable antitumor activity in first-line non-small cell lung cancer (搜索) (NSCLC). The results were presented in an oral session at the 2026 World Conference on Lung Cancer (WCLC).
Efficacy Across the Overall Population
As of the July 1, 2026 data cutoff, 63 treatment-naïve patients had been enrolled, comprising 31 with non-squamous and 32 with squamous NSCLC (搜索). More than 90% had Stage IV disease, and a considerable proportion presented with multiple metastases, including brain and liver metastases. Median follow-up was 7.1 months.
Among 62 efficacy-evaluable patients, the objective response rate (ORR) was 71.0%, the disease control rate (DCR) was 95.2%, and the six-month progression-free survival (PFS) rate was 70.6%.
The enrolled population was notably enriched for low PD-L1 (搜索) expression: PD-L1 TPS ≥1% was observed in only 35.5% of non-squamous and 43.8% of squamous patients, well below the 60%–70% seen in the general NSCLC population.
Squamous NSCLC: Consistent Benefit Regardless of PD-L1
In squamous NSCLC (搜索), opamtistomig (搜索) plus chemotherapy achieved an ORR of 87.1%, a DCR of 96.8%, and a six-month PFS rate of 86.7%. Efficacy was comparable regardless of PD-L1 (搜索) expression, with ORRs of 84.6% in PD-L1-positive and 88.2% in PD-L1-negative patients, and six-month PFS rates of 84.6% and 87.4%, respectively.
Non-Squamous NSCLC: Deep Responses in PD-L1-Positive Disease
Among PD-L1 (搜索)-positive patients with non-squamous NSCLC (搜索), the combination achieved an ORR of 81.8%, a DCR of 100.0%, and a six-month PFS rate of 90.0%. Substantial responses were also observed in patients with low PD-L1 expression (TPS 1%–49%).
Safety Profile
The treatment demonstrated a manageable safety profile generally consistent with PD-(L)1 antibody-based chemotherapy combinations, with no new safety signals observed.
Investigator Commentary
Dr. Charles Cai, Chief Medical Officer of Leads Biolabs (搜索), said the updated data were "highly encouraging," noting that with longer follow-up, tumor shrinkage continued to deepen and ORR continued to increase, providing further evidence of the durability of opamtistomig (搜索)'s antitumor activity.
He highlighted the consistent efficacy observed regardless of PD-L1 (搜索) expression in squamous NSCLC (搜索), together with deep and durable responses in PD-L1-positive non-squamous NSCLC, including patients with low PD-L1 expression. "Despite more than 90% of patients having stage IV disease and many presenting with difficult-to-treat metastatic disease, opamtistomig (搜索) plus chemotherapy continued to demonstrate encouraging efficacy and PFS outcomes," Cai said, adding that the company is advancing Phase III development.
Unmet Need in First-Line NSCLC
According to International Agency for Research on Cancer (IARC) data from 2022, there are approximately 2.48 million new lung cancer cases and approximately 1.82 million lung cancer-related deaths worldwide each year. Data published by the National Cancer Center of China indicate approximately 1.18 million new lung cancer cases and approximately 743,000 lung cancer-related deaths in China in 2024. NSCLC accounts for approximately 85% of all lung cancer cases, and roughly 70% of patients with NSCLC in China are diagnosed at an advanced stage.
Patients without actionable genetic alterations such as EGFR (搜索), ALK (搜索) and ROS1 (搜索) rely primarily on immunotherapy combined with chemotherapy. In squamous NSCLC (搜索), actionable alterations are rare and targeted therapies generally cannot be used; commonly used agents such as pemetrexed and bevacizumab are also unsuitable due to efficacy or safety concerns. Although PD-1/PD-L1 (搜索) inhibitors plus chemotherapy have expanded options, prognosis in squamous NSCLC remains poorer than in non-squamous disease, with a median PFS of only 5 to 8 months and median overall survival of 17 to 27 months.
Mechanism and Development Status
Developed using Leads Biolabs (搜索)' proprietary X-Body bispecific platform, opamtistomig (搜索) is designed to simultaneously block PD-1/PD-L1 (搜索)-mediated immune suppression and conditionally activate 4-1BB (搜索), an agonist pathway, producing a synergistic anti-tumor immune response. Mechanistically, 4-1BB agonism can reactivate exhausted T cells and promote T-cell proliferation, offering promise for PD-1/PD-L1-resistant or immunologically "cold" tumors.
Opamtistomig (搜索) is being evaluated in 14 solid tumor indications, including one pivotal single-arm registrational study, one confirmatory Phase III study, and nine proof-of-concept studies. Clinical evidence has emerged across seven tumor types: extrapulmonary neuroendocrine carcinoma (搜索) (EP-NEC), NSCLC, small cell lung cancer (搜索) (SCLC), biliary tract cancer (搜索) (BTC), hepatocellular carcinoma (搜索) (HCC), esophageal squamous cell carcinoma (搜索) (ESCC), and ovarian cancer (搜索). Approximately 800 patients with solid tumors have been treated to date.
The drug has received Breakthrough Therapy Designation from China's NMPA (October 2024), Orphan Drug Designation from the U.S. FDA (November 2024), and, in January 2026, Fast Track Designation from the FDA and Orphan Drug Designation from the European Commission. In July 2026, its New Drug Application received priority review designation from the NMPA, followed by NDA acceptance in August 2026. Leads Biolabs (搜索) describes opamtistomig (搜索) as the first PD-L1 (搜索)/4-1BB (搜索) bispecific antibody to enter NDA review globally, positioning it as a potential world's first approved 4-1BB-targeting antibody, first approved agonist antibody, and first approved treatment for EP-NEC.
Founded in 2012, Leads Biolabs (搜索) is a clinical-stage biotechnology company with a pipeline of 15 innovative drug candidates, including five clinical-stage candidates and one registration-stage asset. Its proprietary platforms include LeadsBody (CD3 T-cell engager), X-body (4-1BB (搜索) engager), TOPiKinectics (ADC) and ImBiTDC (TDC).