NCT03867084

Safety and Efficacy of Pembrolizumab (MK-3475) Versus Placebo as Adjuvant Therapy in Participants With Hepatocellular Carcinoma (HCC) and Complete Radiological Response After Surgical Resection or Local Ablation (MK-3475-937 / KEYNOTE-937)

Completed Phase 3 Last updated 4 February 2026

What this trial tests

Phase 3 trial testing Pembrolizumab in Hepatocellular Carcinoma in 959 participants. Completed in 30 September 2025.

Timeline

28 May 2019

Primary endpoint
20 March 2025

30 September 2025

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	959
Start date	28 May 2019
Primary completion	20 March 2025
Estimated completion	30 September 2025
Sites	249 locations across Hong Kong, Italy, Japan, Malaysia, Taiwan, Ireland, Poland, South Korea

Drugs / interventions tested

• Pembrolizumab (pembrolizumab) — full drug profile →
• Placebo

Conditions studied

• Hepatocellular Carcinoma — all drugs for Hepatocellular Carcinoma →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Hepatocellular Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This study will evaluate the safety and efficacy of pembrolizumab (MK-3475) versus placebo as adjuvant therapy in participants with hepatocellular carcinoma (HCC) and complete radiological response after surgical resection or local ablation. The primary hypotheses of this study are that adjuvant pembrolizumab is superior to placebo with respect to: 1) recurrence-free survival (RFS) as assessed by blinded independent central review (BICR); and 2) overall survival (OS).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Advances in immunotherapy for hepatocellular carcinoma.
   Sangro B, Sarobe P, Hervás-Stubbs S, Melero I. · · 2021 · cited 1002× · PMID 33850328 · DOI 10.1038/s41575-021-00438-0
2. Tumor Immune Microenvironment and Immunosuppressive Therapy in Hepatocellular Carcinoma: A Review.
   Oura K, Morishita A, Tani J, Masaki T. · · 2021 · cited 340× · PMID 34071550 · DOI 10.3390/ijms22115801
3. Emerging Therapies for Hepatocellular Carcinoma (HCC).
   Chakraborty E, Sarkar D. · · 2022 · cited 236× · PMID 35681776 · DOI 10.3390/cancers14112798
4. Emerging immunotherapy for HCC: A guide for hepatologists.
   Foerster F, Gairing SJ, Ilyas SI, Galle PR. · · 2022 · cited 185× · PMID 35253934 · DOI 10.1002/hep.32447
5. Hepatocellular Carcinoma Immune Landscape and the Potential of Immunotherapies.
   Giraud J, Chalopin D, Blanc JF, Saleh M. · · 2021 · cited 172× · PMID 33815418 · DOI 10.3389/fimmu.2021.655697
6. Inflammatory Mechanisms of HCC Development.
   Refolo MG, Messa C, Guerra V, Carr BI, et al · · 2020 · cited 149× · PMID 32164265 · DOI 10.3390/cancers12030641
7. Strategies to Improve the Antitumor Effect of Immunotherapy for Hepatocellular Carcinoma.
   Xing R, Gao J, Cui Q, Wang Q. · · 2021 · cited 136× · PMID 34899747 · DOI 10.3389/fimmu.2021.783236
8. Reshaping the systemic tumor immune environment (STIE) and tumor immune microenvironment (TIME) to enhance immunotherapy efficacy in solid tumors.
   Xu L, Zou C, Zhang S, Chu TSM, et al · · 2022 · cited 131× · PMID 35799264 · DOI 10.1186/s13045-022-01307-2