BioNTech and OncoC4 Report Survival Gain in Phase 3 Lung Cancer Trial

BioNTech and OncoC4 said Monday that updated data from the non-pivotal first stage of their Phase 3 PRESERVE-003 trial showed a median overall survival of 18.5 months for patients who received gotistobart, compared with 10.0 months for those treated with docetaxel. The study is evaluating gotistobart in previously treated metastatic squamous non-small cell lung cancer, a setting in which treatment options are limited after disease progression on immunotherapy and platinum-based chemotherapy.

The updated analysis covered 87 patients in the squamous NSCLC cohort, with 45 assigned to gotistobart and 42 to docetaxel. At a July 17 data cutoff and median follow-up of 25.4 months, the hazard ratio for death was 0.56 and the companies reported a nominal p-value of 0.0295. BioNTech and OncoC4 characterized the result as a clinically meaningful overall-survival benefit, but the readout comes from the trial’s non-pivotal stage 1, not from the ongoing pivotal stage that is intended to provide the confirmatory evidence needed for a potential regulatory filing.

BioNTech disclosed the updated results in a Sept. 14 Form 6-K and accompanying release after the data were presented at the IASLC 2026 World Conference on Lung Cancer. The filing also said the safety profile remained consistent with earlier reports. Grade 3 or higher treatment-related adverse events occurred in 44.4% of patients receiving gotistobart and 48.8% of patients receiving docetaxel.

Updated data put a median on the earlier survival signal

The latest readout adds maturity to a result that had already drawn attention earlier this year. In the stage 1 analysis published in Nature Medicine in March, median overall survival had not yet been reached in the gotistobart arm after a median follow-up of 14.5 months, while the docetaxel group had a median survival of 10.0 months. That earlier analysis reported a hazard ratio of 0.46, with a nominal two-sided p-value of 0.0102.

With longer follow-up, the gotistobart median can now be estimated at 18.5 months. The hazard ratio moved from 0.46 to 0.56 as more events accumulated, which is not unusual as a survival dataset matures. The new figure still favors gotistobart, but it is important not to treat the stage 1 result as if it were the final pivotal answer. Stage 1 was designed in part to confirm the dose and assess preliminary efficacy and safety before the study moved into its confirmatory portion.

The treatment schedule used in the updated squamous cohort was gotistobart at 6 mg per kilogram every three weeks, with two 10 mg per kilogram loading doses, versus docetaxel at 75 mg per square meter every three weeks. Overall survival is the central outcome for the program. The earlier peer-reviewed report also showed higher objective response and longer-duration responses with gotistobart than with docetaxel, but those measures remain secondary to the survival question that the pivotal stage is designed to test more definitively.

The pivotal stage remains the key test

PRESERVE-003 is a two-stage, randomized, open-label, active-controlled study. The current ClinicalTrials.gov record lists an estimated enrollment of about 630 participants and describes stage 2 as a one-to-one comparison of the selected gotistobart regimen with docetaxel in squamous NSCLC. BioNTech said the pivotal portion is ongoing at more than 160 sites globally.

The distinction between the stages matters. Stage 1 was non-pivotal and included the dose-confirmation work that established the regimen carried forward. Stage 2 is the part intended to test the survival effect in the larger, confirmatory population. The trial’s primary endpoint is overall survival, while secondary endpoints include objective response rate, progression-free survival and safety.

That structure also limits how far the current 18.5-month figure should be extrapolated. The result comes from 87 patients in the squamous subgroup and is encouraging, but a larger confirmatory dataset can produce a different estimate of treatment effect. The companies themselves framed the stage 1 findings as evidence supporting continued development rather than as a completed registration result. Until the pivotal data are available, gotistobart remains investigational and has not been established as a replacement for docetaxel in this treatment setting.

The ClinicalTrials.gov record currently lists an estimated primary-completion date of Aug. 31, 2027, with estimated study completion in August 2028. Those registry dates can change as a study progresses, and BioNTech’s latest release did not announce a new timing for the pivotal overall-survival readout.

Gotistobart is a major part of BioNTech’s oncology push

Gotistobart, also known as BNT316 or ONC-392, is a pH-sensitive monoclonal antibody targeting CTLA-4. The drug is designed to enhance depletion of regulatory T cells inside the tumor microenvironment while allowing CTLA-4 to recycle back to the cell surface. BioNTech and OncoC4 are pursuing the approach as a way to preserve checkpoint function in peripheral tissues while strengthening anti-tumor immune activity where the tumor is located.

The program has accumulated several regulatory designations. The U.S. Food and Drug Administration granted Fast Track designation in 2022 for metastatic NSCLC that progressed after prior anti-PD-(L)1 therapy, and gotistobart later received Orphan Drug Designation for squamous NSCLC. China’s National Medical Products Administration also granted Breakthrough Therapy Designation for the squamous NSCLC indication in 2025.

BioNTech and OncoC4 began their collaboration in 2023. OncoC4 received a $200 million upfront payment and became eligible for development, regulatory and commercial milestone payments as well as double-digit tiered royalties. The companies agreed to share development costs for gotistobart as monotherapy and in certain PD-1 or PD-L1 combinations through regulatory authorization, while BioNTech holds exclusive worldwide commercialization rights under the collaboration.

For BioNTech, the updated survival result adds another data point to a late-stage oncology portfolio that the company has been expanding beyond its COVID-19 vaccine business. The immediate clinical question is narrower: whether the survival advantage seen in the non-pivotal stage can hold up in the larger pivotal population. That stage 2 overall-survival analysis is now the next decisive milestone for the lung-cancer program.