Table 2.

Ongoing Phase III Trials with Anti-PD-1 Agents for First-Line Advanced Disease

Target Population	Confirmed Pathologic or Radiologicala Diagnosis of HCC; BCLC B Unsuitable for Locoregional Therapy or BCLC C; No Prior Systemic Therapy for HCC; Child-Pugh Class A; ECOG PS 0–1.
Trial Name [Reference] Number	Phase	Study Regimens	Estimated Sample Size	Status	Primary Endpoints	Secondary Endpoints
RATIONALE-301b [36] NCT03412773	III	Tislelizumab 200 mg iv q3w	674	Active, not recruiting	OS	ORR, PFS, DOR, TTP, HRQoL, DCR, CBR
		Sorafenib (800mg/day)
LEAP-002 [40] NCT03713593	III	Pembrolizumab 200 mg iv q3w plus Lenvatinib (12 mg/day or 8 mg/day according to body weight ≥ or < 60 kg)	750	Active, not recruiting	PFS, OS	ORR, DOR, DCR and TTP both per RECIST 1.1 and mRECIST, PFS per mRECIST, lenvatinib pharmacokinetics, safety
		Lenvatinib plus a matching-placebo
CheckMate 9DW NCT04039607	III	Nivolumab 1 mg/kg plus Ipilimumab 3 mg/kg x 4 q3w followed by Nivolumab 480 mg q4w	1084	Recruiting	OS	ORR, DOR, TTSD
		Sorafenib (800 mg/day) or Lenvatinib (12 mg/day or 8 mg/day according to body weight ≥ or < 60 kg)

Notes: ^aA radiological diagnosis according to the American Association for the Study of Liver Diseases (AASLD) criteria is admitted in LEAP-002 trials for cirrhotic patients; ^bnon inferiority trial; references are reported in square brackets.

Abbreviations: HCC, hepatocellular carcinoma; BCLC, Barcelona Clinic Liver Cancer; ECOG PS, Eastern Cooperative Oncology Group Performance Status; iv, intravenously; q3w, every 3 weeks; OS, overall survival; ORR, objective response rate; PFS, progression-free survival; DOR, duration of response; TTP, time to progression; HRQoL, health-related quality of life; DCR, disease control rate; CBR, clinical benefit rate; RECIST 1.1, response evaluation criteria in solid tumors version 1.1; mRECIST, modified response evaluation criteria in solid tumors; q4w, every 4 weeks; TTSD, time to symptom deterioration.