Gotistobart Nearly Doubles Median OS vs Docetaxel in Squamous NSCLC

Gotistobart (BNT316/ONC-392) nearly doubled median overall survival (OS) vs docetaxel in patients with previously treated squamous non–small cell lung cancer (NSCLC), according to updated data from stage 1 of the phase 3 PRESERVE-003 trial (NCT05671510) presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer.¹ The OS benefit was statistically significant and clinically meaningful.

Study Design

PRESERVE-003 is a 2-stage, open-label trial evaluating gotistobart monotherapy vs docetaxel in patients with squamous NSCLC whose disease progressed on anti–PD-(L)1 inhibitors and platinum-based chemotherapy.1 At a data cutoff of July 17, 2026, with a median follow-up of 25.4 months, 87 patients in the nonpivotal stage 1 population had been randomized 1:1 to gotistobart, dosed at 6 mg/kg with two 10 mg/kg loading doses (n = 45), or docetaxel, dosed at 75 mg/m2 (n = 42), in the second-line or later setting. OS was the primary end point; secondary end points include overall response rate, progression-free survival, and safety.

Efficacy and Safety

Median OS was 18.5 months with gotistobart vs 10.0 months with docetaxel (HR, 0.56; nominal P = .0295). Grade 3 or higher treatment-related adverse events occurred in 20 of 45 patients (44.4%) who received gotistobart vs 20 of 42 patients (48.8%) who received docetaxel. The safety profile was manageable and consistent with previously reported data.

Clinical Context and Limitations

Gotistobart is a pH-sensitive, CTLA-4–targeting monoclonal antibody designed to selectively deplete regulatory T cells within the tumor microenvironment while sparing peripheral CTLA-4 signaling. Earlier stage 1 findings from PRESERVE-003, published in Nature Medicine, similarly showed a clinically meaningful OS benefit for gotistobart vs docetaxel in this population. The pivotal stage 2 portion of the trial is ongoing at more than 160 sites globally; squamous NSCLC has a 5-year relative survival rate of 15% and a historical median OS of 11 months in the US.

"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 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,” said Rama Balaraman, MD, principal investigator and medical oncologist, Ocala Oncology Center, Florida, in a news release.

Gotistobart previously received FDA fast track designation in 2022 for metastatic NSCLC that progressed on prior anti–PD-(L)1 therapy and orphan drug designation in 2026 for squamous NSCLC.²

REFERENCES

1. BioNTech and OncoC4 present updated data showing gotistobart nearly doubled median overall survival versus standard-of-care chemotherapy in previously treated squamous non-small cell lung cancer patients. News release. BioNTech SE; OncoC4, Inc. September 14, 2026. Accessed September 14, 2026. https://tinyurl.com/yu55thvt

2. BioNTech and OncoC4 receive FDA orphan drug designation for gotistobart in squamous non-small cell lung cancer. News release. BioNTech. January 12, 2026. Accessed September 14, 2026. https://tinyurl.com/4747bfbd