BioNTech and OncoC4 Report 54% Reduction in Death Risk with Gotistobart in Advanced Squamous Lung Cancer
核心洞察
Gotistobart (BNT316/ONC-392) demonstrated a 54% reduction in death risk compared to standard chemotherapy in patients with metastatic squamous non-small cell lung cancer (搜索) who progressed on prior immunotherapy.
The median overall survival has not been reached for gotistobart patients at 14.5 months follow-up, while chemotherapy patients achieved a median survival of 10 months.
The tumor microenvironment-selective Treg depletion candidate showed manageable safety with 42.2% of patients experiencing grade ≥3 treatment-related adverse events versus 48.8% with docetaxel.
BioNTech and OncoC4 (搜索) announced promising results from the non-pivotal stage of their global Phase 3 trial PRESERVE-003, showing that gotistobart (BNT316/ONC-392) reduced the risk of death by 54% compared to standard chemotherapy in patients with metastatic squamous non-small cell lung cancer (搜索) (sqNSCLC) who had progressed on prior immunotherapy and platinum-based chemotherapy. The data were presented at the IASLC ASCO 2025 North America Conference on Lung Cancer in Chicago.
Significant Survival Benefit Observed
The analysis included 87 patients with sqNSCLC randomized to receive either gotistobart 6 mg/kg with two 10 mg/kg loading doses (N=45) or docetaxel 75 mg/m² (N=42). At a median follow-up of 14.5 months, patients in the gotistobart treatment arm had not yet reached the median overall survival, while the docetaxel treatment arm achieved a median overall survival of 10 months.
The 12-month overall survival rate was 63.1% for gotistobart compared to 30.3% for docetaxel. The hazard ratio for death was 0.46 (95% CI: 0.25-0.84; nominal p-value 0.0102), representing a 54% reduction in the risk of death.
"We are encouraged by the median overall survival still not being reached for patients treated with gotistobart at almost 15 months of follow-up," said Byoung Chul Cho, M.D., Ph.D., Lead Investigator and Professor at the Division of Medical Oncology, Yonsei Cancer Center, Seoul.
Manageable Safety Profile
The safety profile of gotistobart was consistent with previously established data and remained manageable. Grade ≥3 treatment-related adverse events were reported in 19/45 (42.2%) patients in the gotistobart treatment arm versus 20/41 (48.8%) patients in the docetaxel treatment arm.
Novel Mechanism of Action
Gotistobart is a tumor microenvironment-selective regulatory T cell (Treg) depletion candidate targeting CTLA-4 (搜索). As a pH-sensitive monoclonal antibody, gotistobart is designed to enable CTLA-4 protein recycling. After binding to the CTLA-4 receptor on the cell surface, the complex is internalized, and the pH change causes the antibody to unbind, allowing CTLA-4 to return to the surface to preserve the immune checkpoint function at peripheral organs and to enhance anti-tumor immunity in the tumor microenvironment.
"Gotistobart is designed to selectively deplete tumor-infiltrating regulatory T cells within the tumor microenvironment," said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. "The data presented today showed encouraging signals for our approach to translating our deep understanding of the immune system into meaningful survival benefits for patients with squamous NSCLC."
Addressing Unmet Medical Need
Advanced squamous NSCLC remains an aggressive and difficult-to-treat cancer with a median survival of less than a year. Around 25% of all lung cancer cases are attributed to the subtype squamous cell carcinoma. With a 5-year relative survival rate of 15% and a median overall survival of 11 months in the United States (2000-2017), sqNSCLC is a devastating disease with limited treatment options.
"Gotistobart represents a step forward in our goal of offering a chemotherapy-free treatment option for patients with advanced squamous NSCLC, a population with limited therapeutic choices and a lack of actionable biomarkers to guide treatment," said Pan Zheng, M.D., Ph.D., Chief Medical Officer and Co-Founder at OncoC4 (搜索).
Regulatory Recognition and Ongoing Development
Gotistobart has received Fast Track Designation from the U.S. Food and Drug Administration in 2022 for the treatment of patients with metastatic NSCLC (搜索) whose disease progressed on prior anti-PD-(L)1 therapy and Breakthrough Therapy Designation from China's National Medical Products Administration in 2025.
The pivotal stage of the Phase 3 trial is ongoing in more than 160 sites globally, with approximately 500 patients planned to be enrolled at clinical sites in various countries including Australia, Belgium, Canada, China, Germany, Italy, the Netherlands, Spain, South Korea, Türkiye, the United Kingdom and the United States. The primary endpoint is overall survival, with secondary endpoints including overall response rate, progression-free survival and safety profile.
Multiple other trials are ongoing, including a Phase 2 trial in patients with platinum-resistant ovarian cancer (搜索), a Phase 2 trial in patients with metastatic castration-resistant prostate cancer (搜索), and a Phase 1/2 open-label dose escalation trial in patients with advanced solid tumors. BioNTech also evaluates gotistobart in combination with its mRNA cancer immunotherapy candidate BNT116.