{"entity":{"id":"paper-nivolumab-hcc-jama-oncol-2020","kind":"paper","name":"Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Sorafenib: The CheckMate 040 Randomized Clinical Trial","aka":[],"tldr":"Phase 2 or 3 results paper on Nivolumab in Hepatocellular carcinoma, in JAMA Oncology (2020), one of the most cited Europe PMC records with Nivolumab in its title.","summary":"Importance: Most patients with hepatocellular carcinoma (HCC) are diagnosed with advanced disease not eligible for potentially curative therapies; therefore, new treatment options are needed. Combining nivolumab with ipilimumab may improve clinical outcomes compared with nivolumab monotherapy.\n\nObjective: To assess efficacy and safety of nivolumab plus ipilimumab in patients with advanced HCC who were previously treated with sorafenib.\n\nDesign, setting, and participants: CheckMate 040 is a multicenter, open-label, multicohort, phase 1/2 study. In the nivolumab plus ipilimumab cohort, patients were randomized between January 4 and September 26, 2016. Treatment group information was blinded after randomization. Median follow-up was 30.7 months. Data cutoff for this analysis was January 2019. Patients were recruited at 31 centers in 10 countries/territories in Asia, Europe, and North America. Eligible patients had advanced HCC (with/without hepatitis B or C) previously treated with sorafenib. A total of 148 patients were randomized (50 to arm A and 49 each to arms B and C).\n\nInterventions: Patients were randomized 1:1:1 to either nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, administered every 3 weeks (4 doses), followed by nivolumab 240 mg every 2 weeks (arm A); nivolumab 3 mg/kg plus ipilimumab 1 mg/kg, administered every 3 weeks (4 doses), followed by nivolumab 240 mg every 2 weeks (arm B); or nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks (arm C).\n\nMain outcomes and measures: Coprimary end points were safety, tolerability, and objective response rate. Duration of response was also measured (investigator assessed with the Response Evaluation Criteria in Solid Tumors v1.1).\n\nResults: Of 148 total participants, 120 were male (81%). Median (IQR) age was 60 (52.5-66.5). At data cutoff (January 2019), the median follow-up was 30.7 months (IQR, 29.9-34.7). Investigator-assessed objective response rate was 32% (95% CI, 20%-47%) in arm A, 27% (95% CI, 15%-41%) in arm B, and 29% (95% CI, 17%-43%) in arm C. Median (range) duration of response was not reached (8.3-33.7+) in arm A and was 15.2 months (4.2-29.9+) in arm B and 21.7 months (2.8-32.7+) in arm C. Any-grade treatment-related adverse events were reported in 46 of 49 patients (94%) in arm A, 35 of 49 patients (71%) in arm B, and 38 of 48 patients (79%) in arm C; there was 1 treatment-related death (arm A; grade 5 pneumonitis).\n\nConclusions and relevance: In this randomized clinical trial, nivolumab plus ipilimumab had manageable safety, promising objective response rate, and durable responses. The arm A regimen (4 doses nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks then nivolumab 240 mg every 2 weeks) received accelerated approval in the US based on the results of this study.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT01658878.\n\nIndexed on Europe PMC as PubMed record 33001135 (DOI 10.1001/jamaoncol.2020.4564). Its title names Nivolumab and its text names Hepatocellular carcinoma; PubMed types it as a clinical trial report (Clinical Trial, Phase II, research-article, Multicenter Study, Clinical Trial, Phase I, Randomized Controlled Trial). It was matched automatically to the idea \"Immunotherapy downstaging to transplant with a safe washout\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA Oncol 2020","url":"https://doi.org/10.1001/jamaoncol.2020.4564"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33001135/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/33001135"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2020,"doi":"10.1001/jamaoncol.2020.4564","pmid":"33001135","authors":"Yau T, Kang YK, Kim TY, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Nivolumab in Hepatocellular carcinoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Nivolumab in the title and Hepatocellular carcinoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},"route":"/key-papers/paper-nivolumab-hcc-jama-oncol-2020/","neighbours":{"journal":[{"id":"jama-oncology","kind":"journal","name":"JAMA Oncology","route":"/journals/jama-oncology/"}],"idea":[{"id":"idea-hcc-io-before-transplant","kind":"idea","name":"Immunotherapy downstaging to transplant with a safe washout","route":"/ideas/idea-hcc-io-before-transplant/"}]}}