Gotistobart or docetaxel in metastatic squamous non-small cell lung cancer: stage 1 of the randomized phase 3 PRESERVE-003 trial

PRESERVE-003 is a two-stage phase 3 trial evaluating gotistobart (BNT316/ONC-392), a novel pH-sensitive anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibody that selectively depletes regulatory T cells within the tumor microenvironment, in patients with metastatic squamous non-small cell lung cancer (sqNSCLC) without actionable genomic alterations who progressed on programmed cell death protein/programmed death ligand 1 inhibitor/platinum-based chemotherapy-a population with a poor prognosis. Here we report on stage 1, which aimed to confirm the dose and assess the preliminary efficacy (primary outcome: overall survival; secondary outcomes: progression‑free survival, objective response rate and duration of response) and safety of gotistobart compared to docetaxel. Patients with sqNSCLC were randomized (1:1) to gotistobart (6 mg kg<sup>-1</sup> with two 10 mg kg<sup>-1</sup> loading doses every 3 weeks (N = 45)) or docetaxel (75 mg m<sup>-</sup><sup>2</sup> every 3 weeks (N = 42)). After a median follow-up of 14.5 months, median overall survival was not reached with gotistobart (95% confidence interval (CI) 9.3 to not evaluable) versus 10.0 months (95% CI 6.2 to 11.9 months) with docetaxel (hazard ratio 0.46, 95% CI 0.25 to 0.84, nominal two-sided P = 0.0102). Safety was manageable, with grade ≥3 treatment-related adverse events in 42% and 49% of patients receiving gotistobart and docetaxel, respectively. Stage 1 results suggest that gotistobart monotherapy can provide clinically meaningful benefit for patients with programmed cell death protein/programmed death ligand 1-resistant and chemotherapy-resistant metastatic sqNSCLC. ClinicalTrials.gov identifier: NCT05671510 .

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Journal
Nature Medicine
Published
2026-03-27
DOI
https://doi.org/10.1038/s41591-026-04323-8
Primary Topic
Cancer Immunotherapy and Biomarkers
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article
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article

Gotistobart or docetaxel in metastatic squamous non-small cell lung cancer: stage 1 of the randomized phase 3 PRESERVE-003 trial

Michael J. Wenger, Ardalan Davarifar, Meili Sun, Fadi Kayali et al.
Nature Medicine
Cancer Immunotherapy and Biomarkers
article

Gotistobart or docetaxel in metastatic squamous non-small cell lung cancer: stage 1 of the randomized phase 3 PRESERVE-003 trial

Michael J. Wenger, Ardalan Davarifar, Meili Sun, Fadi Kayali, Andrew L. Beardsley, Sergey Efuni, Svetlana Shpyro, X. Wang, Jennifer L. Leddon, Vikram Jain, Mark A. Socinski, Adewale Fawole, J. Hamm, Kun He, Luchun Li, George Zhang, Rama Balaraman, Pan P, B. Yang, Q. Wang, P. Zheng, Y. Huang, Yan Yu, Keon-Uk Park, Tianhong Li, Zhi-gang Liu, Uğur Şahin, Long Wu, Preet Singh, Byoung Chul Cho, Kai He, Ki Hyeong Lee, Lin Wu, Youngjoo Lee, Yang Liu, Yi-Long Wu, Hua-Jun Chen, Xinmin Yu, Shiling Song
article en

Abstract

PRESERVE-003 is a two-stage phase 3 trial evaluating gotistobart (BNT316/ONC-392), a novel pH-sensitive anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibody that selectively depletes regulatory T cells within the tumor microenvironment, in patients with metastatic squamous non-small cell lung cancer (sqNSCLC) without actionable genomic alterations who progressed on programmed cell death protein/programmed death ligand 1 inhibitor/platinum-based chemotherapy-a population with a poor prognosis. Here we report on stage 1, which aimed to confirm the dose and assess the preliminary efficacy (primary outcome: overall survival; secondary outcomes: progression‑free survival, objective response rate and duration of response) and safety of gotistobart compared to docetaxel. Patients with sqNSCLC were randomized (1:1) to gotistobart (6 mg kg<sup>-1</sup> with two 10 mg kg<sup>-1</sup> loading doses every 3 weeks (N = 45)) or docetaxel (75 mg m<sup>-</sup><sup>2</sup> every 3 weeks (N = 42)). After a median follow-up of 14.5 months, median overall survival was not reached with gotistobart (95% confidence interval (CI) 9.3 to not evaluable) versus 10.0 months (95% CI 6.2 to 11.9 months) with docetaxel (hazard ratio 0.46, 95% CI 0.25 to 0.84, nominal two-sided P = 0.0102). Safety was manageable, with grade ≥3 treatment-related adverse events in 42% and 49% of patients receiving gotistobart and docetaxel, respectively. Stage 1 results suggest that gotistobart monotherapy can provide clinically meaningful benefit for patients with programmed cell death protein/programmed death ligand 1-resistant and chemotherapy-resistant metastatic sqNSCLC. ClinicalTrials.gov identifier: NCT05671510 .

Nature Medicine
Central South University (CN), Harbin Medical University (CN), Yonsei University (KR), Norton Healthcare (US), The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US), University of Tennessee Medical Center (US), University of the Potomac (US), Wuhan University (CN), Florida Hospital Cancer Institute (US), Third Affiliated Hospital of Southern Medical University (CN), Zhejiang Cancer Hospital (CN), Third Affiliated Hospital of Harbin Medical University (CN), Jinan Central Hospital (CN), Hunan Cancer Hospital (CN), Florida Cancer Specialists & Research Institute (US), First Affiliated Hospital of Guangdong Pharmaceutical University (CN), National Cancer Center (KR), Cardiovascular Institute of Central Florida (US), Hainan General Hospital (CN), Oncoceutics (United States) (US), BioNTech (Germany) (DE), AdventHealth Tampa (US), Renmin Hospital of Wuhan University (CN), TCM-Intigrated Cancer Center of Southern Medical University (CN), Seventh People's Hospital of Shanghai (CN), Guangdong Academy of Medical Sciences (CN), Cancer Care of Western North Carolina (US), Springfield Clinic (US), Chongqing Cancer Hospital (CN), BioNTech (United States) (US), Xiangya Hospital Central South University (CN), Hubei Cancer Hospital (CN), UC Davis Health (US), Chungbuk National University Hospital (KR), Mater Adult Hospital (AU), Keimyung University (KR), Southern Medical University (CN), University of Cincinnati (US), University of Tennessee at Knoxville (US)
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