Gotistobart Nearly Doubles Median Overall Survival in Previously Treated Squamous NSCLC in Phase 3 PRESERVE-003 Stage 1
核心洞察
BioNTech and OncoC4 (搜索) reported median overall survival of 18.5 months with gotistobart versus 10.0 months with docetaxel in stage 1 of the Phase 3 PRESERVE-003 trial.
The CTLA-4 (搜索)-targeting immunotherapy produced a hazard ratio of 0.56 with a nominal p-value of 0.0295 in 87 patients with metastatic squamous NSCLC.
Grade 3 or higher treatment-related adverse events occurred in 44.4% of gotistobart patients versus 48.8% of docetaxel patients, consistent with prior safety data.
BioNTech SE and OncoC4 (搜索), Inc. reported that gotistobart (BNT316/ONC-392) nearly doubled median overall survival compared with standard-of-care chemotherapy in patients with squamous non-small cell lung cancer (搜索) (NSCLC) whose disease progressed on prior immunotherapy and chemotherapy. The first median overall survival data from the non-pivotal stage 1 of the global randomized PRESERVE-003 Phase 3 trial (NCT05671510) were presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC) and announced on September 14, 2026.
At the data cut-off on July 17, 2026, with a median follow-up of 25.4 months, 87 patients with metastatic squamous NSCLC had been randomized to receive either gotistobart monotherapy 6 mg/kg with two 10 mg/kg loading doses (N=45) or docetaxel 75 mg/m² (N=42) in the second-line or later treatment setting. Median overall survival was 18.5 months for patients treated with gotistobart compared with 10.0 months for those treated with docetaxel (HR: 0.56; nominal p-value=0.0295). The companies characterized the benefit as statistically significant and clinically meaningful.
Safety Profile Consistent With Prior Data
The safety profile of gotistobart was consistent with previously reported data and remained manageable, according to the companies. Grade ≥3 treatment-related adverse events were reported in 20/45 (44.4%) patients receiving gotistobart and 20/42 (48.8%) patients receiving docetaxel.
A Tumor Microenvironment-Selective CTLA-4 Approach
Gotistobart is an investigational CTLA-4 (搜索)-targeting immunotherapy designed to selectively deplete regulatory T cells (搜索) (Tregs) within the tumor microenvironment and restore anti-tumor immune activity. As a pH-sensitive monoclonal antibody, it 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 immune checkpoint function at peripheral organs while enhancing anti-tumor immunity in the tumor microenvironment.
"The data support the differentiated mechanism of action of gotistobart as a tumor microenvironment-selective Treg modulator and reinforce our confidence in the therapeutic potential of this distinct CTLA-4 (搜索)-targeting approach to meaningfully shift the treatment landscape in this indication," said Pan Zheng, M.D., Ph.D., Co-Founder and Chief Medical Officer at OncoC4 (搜索).
Investigators Point to an Unmet Need in Second-Line Disease
"Patients with squamous NSCLC continue to face limited treatment options after progression on immunotherapy. Current survival expectations with established therapies remain less than a year, and despite numerous development efforts, chemotherapy has remained the standard of care in this setting for more than a decade," said Rama Balaraman, M.D., Principal Investigator and medical oncologist at Ocala Oncology Center, Florida, United States. "The magnitude of the survival benefit observed with gotistobart as a chemotherapy-free treatment approach in the PRESERVE-003 clinical trial is highly encouraging. If confirmed in the pivotal portion of the Phase 3 trial, these findings could transform the standard of care in a setting where new therapies are urgently needed."
Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech, framed the result in the context of acquired resistance: "In second- and later lines of treatment, the clinical relevance of novel therapeutic options depends on the ability to re-engage a suppressed or exhausted anti-tumor immune response and overcome acquired resistance. This update highlights gotistobart's unique mode of action and our ambition to translate our deep understanding of the immune system into meaningful survival benefit for patients with lung cancer – particularly in areas where patients still need more."
Trial Design and Prior Data
PRESERVE-003 (NCT05671510; EUCT:2023-505311-20-01; CTR20232927) is a two-stage, open-label Phase 3 trial evaluating the efficacy and safety of gotistobart as monotherapy compared with standard-of-care docetaxel in squamous NSCLC patients who have progressed on PD-(L)1 (搜索) inhibitors and platinum-based chemotherapy. The non-pivotal stage of the trial included all NSCLC patients, while the ongoing pivotal stage enrolled patients with squamous NSCLC. The primary endpoint is overall survival; secondary endpoints include overall response rate, progression-free survival, and safety profile.
The pivotal stage 2 portion of PRESERVE-003 is currently ongoing at more than 160 sites globally. Gotistobart previously demonstrated a clinically meaningful overall survival benefit and durable anti-tumor activity versus docetaxel in stage 1 of the trial in patients with squamous NSCLC who had progressed on PD-(L)1 (搜索) inhibitors; that data were published in Nature Medicine and presented at the 2026 European Lung Cancer Congress and the IASLC ASCO 2025 North America Conference on Lung Cancer.
Disease Burden and Regulatory Status
Squamous NSCLC carries a 5-year relative survival rate of 15% and a median overall survival of 11 months in the United States (2000–2017). Current standard of care includes surgery and radiotherapy in combination with chemotherapy, and treatment options for second-line therapy after first-line immunotherapy and chemotherapy are limited to chemotherapy or palliative therapy in advanced/metastatic squamous NSCLC, remaining more limited than for non-squamous NSCLC.
Gotistobart received Fast Track Designation from the U.S. Food and Drug Administration in 2022 for patients with metastatic NSCLC whose disease progressed on prior anti-PD-(L)1 (搜索) therapy, and Orphan Drug Designation for squamous NSCLC in 2025. China's National Medical Products Administration granted Breakthrough Therapy Designation in 2025. The candidate is being jointly developed by BioNTech and OncoC4 (搜索) and is in late-stage clinical development as a monotherapy and as a component of combination therapy across multiple cancer indications.