On September 14, 2026 BioNTech SE (Nasdaq: BNTX, "BioNTech") and OncoC4, Inc. ("OncoC4") reported the first median overall survival ("OS") data from the non-pivotal stage 1 of the global randomized PRESERVE-003 Phase 3 clinical trial (NCT05671510) of gotistobart (also known as BNT316 or ONC-392), in patients with squamous non-small lung cancer ("NSCLC") whose disease progressed on prior immunotherapy and chemotherapy. Gotistobart is an investigational CTLA-4-targeting immunotherapy designed to selectively deplete regulatory T cells ("Tregs") within the tumor microenvironment and restore anti-tumor immune activity.
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The data showed that treatment with gotistobart led to a statistically significant and clinically meaningful OS benefit, nearly doubling survival compared with standard-of-care chemotherapy in this patient population. The data were presented at the International Association for the Study of Lung Cancer ("IASLC") 2026 World Conference on Lung Cancer ("WCLC").
"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."
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. The median OS was 18.5 months for patients treated with gotistobart compared to 10.0 months for patients treated with docetaxel (HR: 0.56; nominal p-value=0.0295). The safety profile of gotistobart was consistent with previously reported data and remained manageable. Grade ≥3 treatment-related adverse events ("AEs") were reported in 20/45 (44.4%) patients receiving gotistobart and 20/42 (48.8%) patients receiving docetaxel.
"These data underscore gotistobart’s potential to redefine treatment for patients with hard-to-treat squamous NSCLC whose disease has progressed after initial therapy and who face limited options," said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. "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. We look forward to continuing our work with our colleagues at OncoC4 to further explore and realize gotistobart’s full potential."
"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-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. "We are encouraged by the clinical activity and safety profile observed to date and remain focused on advancing gotistobart for patients with this difficult-to-treat disease."
The pivotal stage 2 portion of PRESERVE-003 is currently ongoing at more than 160 sites globally. Gotistobart previously demonstrated a clinically meaningful OS benefit and durable anti-tumor activity versus docetaxel in stage 1 of the PRESERVE-003 Phase 3 trial in patients with squamous NSCLC who had progressed on PD-(L)1 inhibitors. This data was published in Nature Medicine and presented at the 2026 European Lung Cancer Congress ("ELCC") and the IASLC ASCO (Free ASCO Whitepaper) 2025 North America Conference on Lung Cancer ("NACLC").
About the PRESERVE-003 clinical trial
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 to the standard-of-care chemotherapy (docetaxel) in squamous NSCLC patients, who have progressed on PD-(L)1 inhibitors and platinum-based chemotherapy. The non-pivotal stage of the trial included all NSCLC patients. 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.
About gotistobart (BNT316/ONC-392)
Gotistobart (BNT316/ONC-392) is an investigational immunotherapy that enhances Treg depletion within the tumor microenvironment through targeting CTLA-4 to reignite antitumor immunity and which is being jointly developed by BioNTech and OncoC4.2,3,4,5,6,7,8,9 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.9
Gotistobart is currently in late-stage clinical development as a monotherapy and as a component of combination therapy in various cancer indications. Gotistobart received Fast Track Designation from the U.S. Food and Drug Administration ("FDA") in 2022 for the treatment of patients with metastatic NSCLC whose disease progressed on prior anti-PD-(L)1 therapy and Orphan Drug Designation for the treatment of patients with squamous NSCLC in 2025. The candidate also received Breakthrough Therapy Designation from China’s National Medical Products Administration ("NMPA") in 2025.
About squamous non-small cell lung cancer
With a 5-year relative survival rate of 15% and a median overall survival of 11 months in the United States (2000-2017), squamous NSCLC is a devastating disease with limited treatment options.1 Current standard-of-care includes surgery and radiotherapy in combination with chemotherapy.9 Treatment options for second-line therapy after first-line immunotherapy and chemotherapy are limited to chemotherapy or palliative therapy in advanced/metastatic squamous NSCLC and remain more limited than for non-squamous NSCLC.
(Press release, BioNTech, SEP 14, 2026, View Source [SID1234670815])