OncoC4, Inc. announced it will present pivotal trial design data for PRESERVE-003 at the World Conference on Lung Cancer (WCLC) 2025 in Barcelona, Spain, September 6-9, 2025. The presentation will detail the Stage II design of this potentially registrational Phase 3 study evaluating gotistobart monotherapy compared to docetaxel in squamous non-small cell lung cancer (sqNSCLC) patients after progression on PD-(L)1 inhibitors.
Trial Design and Rationale
PRESERVE-003 (NCT05671510) is a two-stage, randomized, open-label, active-controlled Phase 3 study sponsored by OncoC4. The Stage I dose-confirmation phase assessed two gotistobart dosing regimens (3 mg/kg Q3W and 6 mg/kg Q3W with 2 loading doses of 10 mg/kg Q3W) compared to docetaxel 75 mg/m2 Q3W in patients with squamous and non-squamous NSCLC.
Based on safety, efficacy and exposure-response analyses from Stage I, the data supported selecting the high dose for Stage II, which consists of 1:1 randomization between gotistobart at 6 mg/kg Q3W with 2 loading doses of 10 mg/kg versus docetaxel (75 mg/m2 Q3W) specifically in squamous cell NSCLC patients. The primary endpoint is Overall Survival.
Addressing Critical Unmet Need
Squamous NSCLC represents one of the deadliest cancers with very limited treatment options following traditional chemotherapy and immunotherapy with immune checkpoint inhibitors. The disease makes up 25-30% of all lung cancers and is the most common lung cancer found in smokers. In the US, first-line treatment for metastatic squamous NSCLC commonly involves a combination of chemotherapy and immunotherapy, but treatment choices diminish significantly when patients progress on prior immunotherapy options.
OncoC4 and strategic partner BioNTech selected this indication based on encouraging Phase 1/2 results and the match between the vulnerability of sqNSCLC and gotistobart's mechanism of action.
Next-Generation CTLA-4 Targeting
Gotistobart (BNT316/ONC-392) is a next-generation, acid pH-sensitive anti-CTLA-4 monoclonal antibody candidate engineered to avoid antibody-induced lysosomal target degradation for improved therapeutic index. Combined with modifications in the Fc region, gotistobart induces more potent and selective depletion of regulatory T cells in the tumor microenvironment.
"The mechanism of action of gotistobart has the potential for clinical development of the drug beyond lung cancers for other indications with unmet medical needs, either as monotherapy or in combination with other therapeutic modalities," said Yang Liu, PhD, Co-Founder, CEO, and CSO of OncoC4.
Global Trial Progress
Stage II enrollment continues to progress well with nearly 160 active sites worldwide. Gotistobart is licensed to BioNTech for commercialization and jointly developed clinically by OncoC4 and BioNTech for oncology indications. Several ongoing clinical trials in different tumor types are investigating gotistobart either as monotherapy or in combination with other therapeutic agents.
Conference Presentation Details
The poster presentation titled "PRESERVE-003: A Phase 3 Study of Gotistobart Versus Docetaxel in Metastatic NSCLC After Progression on PD-(L)1 Inhibitors (NCT05671510)" will be presented by Dr. Tianhong Li, Professor in the Department of Internal Medicine, Division of Hematology and Oncology at UC Davis Comprehensive Cancer Center, on Tuesday, September 9, 2025 at 10:00 AM CEST during the P3.18 - Ongoing Clinical Trials session.
