Randomized Phase 3 LEAP-012 Study: Transarterial Chemoembolization With or Without Lenvatinib Plus Pembrolizumab for Intermediate-Stage Hepatocellular Carcinoma Not Amenable to Curative Treatment

Cardiovasc Intervent Radiol. 2022 Apr;45(4):405-412. doi: 10.1007/s00270-021-03031-9. Epub 2022 Feb 4.


Purpose: Transarterial chemoembolization (TACE) is the standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC). Lenvatinib, a multikinase inhibitor, and pembrolizumab, a PD-1 inhibitor, have shown efficacy and tolerability in patients with HCC, and adding this combination to TACE may enhance clinical benefit.

Protocol: LEAP-012 is a prospective, double-blind randomized phase 3 study. Adults with confirmed HCC localized to the liver without portal vein thrombosis and not amenable to curative treatment, ≥ 1 measurable tumor per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1), Eastern Cooperative Oncology Group performance status 0 or 1, Child-Pugh class A and no previous systemic treatment for HCC are eligible. Patients will be randomly assigned to lenvatinib once daily plus pembrolizumab every 6 weeks plus TACE or placebos plus TACE. Dual primary endpoints are overall survival and progression-free survival per RECIST 1.1 by blinded independent central review (BICR). Secondary endpoints are progression-free survival, objective response rate, disease control rate, duration of response and time to progression per modified RECIST by BICR; objective response rate, disease control rate, duration of response and time to progression per RECIST 1.1 by BICR; and safety.

Statistics: The planned sample size, 950 patients, was calculated to permit accumulation of sufficient overall survival events in 5 years to achieve 90% power for the overall survival primary endpoint.

Discussion: LEAP-012 will evaluate the clinical benefit of adding lenvatinib plus pembrolizumab to TACE in patients with intermediate-stage HCC not amenable to curative treatment.

Clinicaltrials: gov NCT04246177.

Keywords: Intermediate-stage hepatocellular carcinoma; Lenvatinib; Pembrolizumab; Transarterial chemoembolization.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized
  • Carcinoma, Hepatocellular* / pathology
  • Chemoembolization, Therapeutic* / adverse effects
  • Humans
  • Liver Neoplasms* / pathology
  • Phenylurea Compounds
  • Prospective Studies
  • Quinolines
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Phenylurea Compounds
  • Quinolines
  • pembrolizumab
  • lenvatinib

Associated data

  • ClinicalTrials.gov/NCT04246177