Journal: Nature medicine
This publication reports stage 1 results of PRESERVE-003, a two-stage phase 3 trial testing gotistobart (BNT316/ONC-392), a pH-sensitive anti-CTLA-4 antibody, in a particularly high-risk group: patients with metastatic squamous NSCLC without targetable alterations who have progressed after prior PD-1/PD-L1 inhibitor plus platinum chemotherapy.
Key design points:
- Population: Metastatic sqNSCLC, PD-1/PD-L1–resistant and platinum-resistant, no actionable genomic alterations.
- Randomization: 1:1 to:
- Gotistobart: 6 mg/kg q3w with two 10 mg/kg loading doses (n=45)
- Docetaxel: 75 mg/m² q3w (n=42)
- Stage 1 objectives: Confirm dose and assess preliminary efficacy (primary outcome: overall survival) and safety. Secondary outcomes: PFS, ORR, duration of response.
Efficacy:
- Median follow-up: 14.5 months.
- Overall survival:
- Gotistobart: median OS not reached (95% CI 9.3 to not evaluable)
- Docetaxel: median OS 10.0 months (95% CI 6.2–11.9)
- Hazard ratio for death: 0.46 (95% CI 0.25–0.84), nominal two-sided P = 0.0102.
- These data indicate a substantial relative reduction in risk of death versus docetaxel in this refractory setting.
Safety:
- Grade ≥3 treatment-related adverse events:
- Gotistobart: 42%
- Docetaxel: 49%
- Overall, safety was considered manageable in both arms.
Clinical interpretation:
- In patients with PD-1/PD-L1–resistant, chemotherapy-resistant metastatic squamous NSCLC, gotistobart monotherapy demonstrated a promising overall survival advantage over docetaxel with a manageable toxicity profile.
- These stage 1 data support continued evaluation of gotistobart in this population and suggest a potential new immunotherapy option after standard chemo-immunotherapy failure.