Gotistobart Doubles Median Survival for Squamous NSCLC Patients

BioNTech and OncoC4 have announced updated data from the PRESERVE-003 Phase 3 clinical trial, showing that their investigational immunotherapy, gotistobart, nearly doubled the median overall survival of patients with previously treated squamous non-small cell lung cancer (NSCLC) compared to standard-of-care chemotherapy.

The trial, which included 87 patients with metastatic squamous NSCLC, demonstrated a median overall survival of 18.5 months for patients treated with gotistobart, compared to 10.0 months for those receiving docetaxel, a standard chemotherapy treatment. The results were presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer.

Gotistobart, also known as BNT316 or ONC-392, is an investigational CTLA-4-targeting immunotherapy designed to selectively deplete regulatory T cells (Tregs) within the tumor microenvironment. This unique mechanism of action is intended to reignite anti-tumor immunity and overcome acquired resistance in patients who have progressed on prior immunotherapy and chemotherapy.

Rama Balaraman, M.D., a principal investigator and medical oncologist at Ocala Oncology Center, emphasized the significance of these findings. "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. The magnitude of the survival benefit observed with gotistobart as a chemotherapy-free treatment approach is highly encouraging."

The updated data from the non-pivotal stage 1 of the trial, which had a median follow-up of 25.4 months, showed that 87 patients were randomized to receive either gotistobart monotherapy (6 mg/kg with two 10 mg/kg loading doses) or docetaxel (75 mg/m2) in the second-line or later treatment setting. The safety profile of gotistobart was consistent with previously reported data and remained manageable. Grade ≥3 treatment-related adverse events were reported in 44.4% of patients receiving gotistobart and 48.8% of patients receiving docetaxel.

Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech, commented, "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."

Pan Zheng, M.D., Ph.D., Co-Founder and Chief Medical Officer at OncoC4, added, "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. 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 the PRESERVE-003 trial 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 inhibitors. This data was published in Nature Medicine and presented at the 2026 European Lung Cancer Congress (ELCC) and the IASLC ASCO 2025 North America Conference on Lung Cancer.

Squamous NSCLC is a devastating disease with limited treatment options, characterized by 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. 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.

BioNTech, a global next-generation biopharmaceutical company, is committed to transforming how cancer is treated. Its pipeline includes complementary treatment approaches spanning immunomodulators, antibody drug conjugates, and mRNA cancer immunotherapies. Gotistobart is currently in late-stage clinical development as a monotherapy and as a component of combination therapy in various cancer indications.