In this largest clinical trial of a neoadjuvant anti-PD-1 monotherapy reported to date in hepatocellular carcinoma, the noted pathological responses to cemiplimab (an anti-PD-1) favor the design of larger trials to determine the optimal treatment duration and definitively establish the clinical advantage of preoperative PD-1 blockade in cases of hepatocellular carcinoma.

• In this single-arm, open-label, phase 2 trial, 21 patients with resectable hepatocellular carcinoma (stage Ib, II, and IIIb) were enrolled; all patients were treated with neoadjuvant cemiplimab, and 20 patients had successful resection (4 [20%] of which had significant tumor necrosis).

• A partial response was achieved in three (15%) of 20 patients, and all other patients maintained stable disease.

• During the neoadjuvant treatment period, a treatment-emergent adverse event of any grade occurred in 20 (95%) patients.

• Elevated aspartate aminotransferase (in four patients), increased blood creatine phosphokinase (in three), constipation (in three), and fatigue (in three) were documented as the most common adverse events of any grade.

• Grade 3 adverse events, including raised blood creatine phosphokinase (in two patients) and hypoalbuminemia (in one), occurred in seven patients.

• Grade 4 or 5 events did not occur, and pneumonitis developed in one patient resulting in a delay in surgery by 2 weeks.