WCLC 2025 - Posters & ePosters-P3.18.39 PRESERVE-003: A Phase 3 Study of Gotistobart Versus Docetaxel in Metastatic NSCLC After Progression on PD-(L)1 Inhibitors

P3.18.39 PRESERVE-003: A Phase 3 Study of Gotistobart Versus Docetaxel in Metastatic NSCLC After Progression on PD-(L)1 Inhibitors

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Pdf Summary

The PRESERVE-003 study (NCT05671510) is a Phase 3, randomized, open-label trial evaluating gotistobart, a novel humanized anti-CTLA-4 monoclonal antibody, versus docetaxel in patients with metastatic non-small cell lung cancer (NSCLC) who have progressed after prior treatment with PD-(L)1 inhibitors. Gotistobart has a unique mechanism that preserves CTLA-4 immune checkpoint activity by avoiding lysosomal degradation, enabling selective depletion of tumor-infiltrating regulatory T cells (Tregs) in the tumor microenvironment without affecting peripheral Tregs. This mechanism may enhance antitumor immunity while reducing immune-related adverse events compared to other anti-CTLA-4 antibodies.<br /><br />The drug showed promising results in the phase 1 study (PRESERVE-001), demonstrating a favorable safety profile and clinical activity with an objective response rate (ORR) of 29.6% and disease control rate (DCR) of 62.9% in patients resistant to immune checkpoint inhibitors, with a lower incidence of severe immune-related adverse events.<br /><br />PRESERVE-003 consists of two stages: Stage I (dose confirmation) enrolling squamous and non-squamous NSCLC, and Stage II (pivotal) focusing on squamous NSCLC with 478 patients randomized 1:1 to gotistobart 6 mg/kg (with two 10 mg/kg loading doses every 3 weeks) or docetaxel 75 mg/m² every 3 weeks. Key eligibility includes adults with metastatic NSCLC who progressed after at least 12 weeks of PD-(L)1 inhibitor therapy combined with platinum chemotherapy, measurable disease, and ECOG 0–1 performance status.<br /><br />Primary endpoint is overall survival (OS); secondary endpoints include ORR, progression-free survival (PFS), and safety. Exploratory analyses cover pharmacokinetics, immunogenicity, and quality of life measures.<br /><br />The trial is global, with approximately 695 patients planned across multiple countries. Enrollment began in June 2023 with expected completion in Q3 2027. Gotistobart is co-developed by OncoC4 and BioNTech. Results could offer a new therapeutic option for NSCLC patients exhibiting resistance to current immunotherapy.

Asset Subtitle

Tianhong Li

Meta Tag

Speaker Tianhong Li

Topic Clinical Trials in Progress

Keywords

PRESERVE-003 study

gotistobart

anti-CTLA-4 monoclonal antibody

metastatic non-small cell lung cancer

PD-(L)1 inhibitor resistance

tumor-infiltrating regulatory T cells depletion

immune checkpoint therapy

phase 3 clinical trial

overall survival endpoint

OncoC4 and BioNTech collaboration