Gotistobart or docetaxel in metastatic squamous non-small cell lung cancer: stage 1 of the randomized phase 3 PRESERVE-003 trial
Year: 2026
Type: article
Study design: Clinical Trial
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 −1 with two 10 mg kg −1 loading doses every 3 weeks ( N = 45)) or docetaxel (75 mg m − 2 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 .
Source: Nature Medicine
Authors: Byoung Chul Cho, Rama Balaraman, Hua-Jun Chen, Xinmin Yu, Adewale Fawole, Zhi-gang Liu, Jiliang Zhang, Long Wu, Long Wu, Bin Yang, Jennifer L. Leddon, John Hamm, Yanjing Huang, Lin Wu, Lin Wu, Pinhua Pan, Preet Singh, Andrew Beardsley, Fadi Kayali, Ardalan Davarifar, Ki Hyeong Lee, Keon-Uk Park, Youngjoo Lee, Luchun Li, Xicheng Wang, Meili Sun, Yan Yu, Vikram Jain, Svetlana Shpyro, Qiong Wang, Michael Wenger, Uğur Şahin, Sergey Efuni, Shiling Song, Kun He, Kun He, Pan Zheng, Yang Liu, Kai He, Kai He, Tianhong Li, Mark A. Socinski, Yi-Long Wu
Institutions: Yonsei Cancer Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Southern Medical University, Zhejiang Cancer Hospital, Florida Cancer Specialists & Research Institute, Dongguan People’s Hospital, Chengdu Seventh People's Hospital, Hunan Cancer Hospital, Renmin Hospital of Wuhan University, Hubei Cancer Hospital, University of Cincinnati, Norton Healthcare, Hainan General Hospital, Xiangya Hospital Central South University, Springfield Clinic, University of Tennessee Medical Center, Chungbuk National University, Chungbuk National University Hospital, Keimyung University Dongsan Hospital, National Cancer Center, Chongqing Cancer Hospital, First Affiliated Hospital of Guangdong Pharmaceutical University, Jinan Central Hospital, Harbin Medical University, Third Affiliated Hospital of Harbin Medical University, Mater Adult Hospital, BioNTech (Germany), BioNTech (United States), The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Pelotonia, The Ohio State University, UC Davis Comprehensive Cancer Center, AdventHealth Orlando, AdventHealth
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funder: National Institutes of Health
OpenAlex ID: W7141500883