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^-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 .