Dostarlimab, an anti‐programmed death‐1 monoclonal antibody, does not cause QT prolongation in patients with solid tumours: A concentration‐QT analysis

Aims Patients with solid tumours were treated with the anti‐PD‐1 antibody dostarlimab in the Phase I GARNET trial. This study aimed to examine dostarlimab's effect on corrected QT (QTc) interval and the systemic concentration–QTc interval relationship. Methods In GARNET Part 2B, patients received 500 mg dostarlimab every 3 weeks (Q3W) for four cycles, then 1000 mg Q6W. Triplicate 12‐lead ECGs were recorded and time‐matched pharmacokinetic (PK) samples collected at screening, on Day 1 of Cycles 1, 4, 5, 8, 12 (pre‐dose and 0.5 h after infusion end), and at treatment end. Concentration–change from baseline QTcF (ΔQTcF) analysis using a linear mixed effects model, summary statistics, incidence of clinically noteworthy ECG values and rhythm abnormalities were evaluated. Results A total of 377 patients were considered for evaluation ( n = 15 excluded from concentration–ΔQTcF). There was a non‐significant concentration–ΔQTcF relationship (0.001589 ms/μg/mL; P = .5906). Mean ΔQTcF increase was <6 ms (upper‐bound two‐sided 90% confidence interval [CI], <10 ms at all post‐dose timepoints). Highest geometric mean concentration was 414.1 μg/mL (Cycle 5 Day 1, 0.5 h) with predicted mean ∆QTcF of 3.064 ms (upper‐bound two‐sided 90% CI: 5.071). Mean QTcF prolongation (all concentrations) was 2.4 ms. QTcF prolongation ≥500 ms occurred in five patients (1.3%); 51 (13.6%) and nine patients (2.4%) had ΔQTcF ≥30 ms and ≥60 ms, respectively. Ten patients (2.7%) reported rhythm abnormalities. No U‐wave abnormalities, torsades de pointes, ventricular tachycardia or ventricular fibrillation/flutter were observed. Conclusions Dostarlimab does not cause clinically significant QTcF prolongation exceeding the regulatory concern threshold.