Evidence map›Paper›PMID 41831609›Full record

ArticleJHEP reports : innovation in hepatology2026

Phase II trial with nivolumab and sorafenib in HCC identified enrichment of immunosuppressive monocytes in patients with Child-Pugh B liver dysfunction.

Bridget P Keenan, Zenghua Fan, Bryan Khuong Le, Quincy Harris, Jocelin Chen, Matthew Clark, Averey Lea, Li Zhang, Alexander Cheung, Frances Lara and 7 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JHEP reports : innovation in hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03439891 (Multicenter Pilot Study of the Safety, Efficacy, and Immune Cell Profiling in Advanced Hepatocellular Carcinoma), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03439891 phase2completednot on this map

Multicenter Pilot Study of the Safety, Efficacy, and Immune Cell Profiling in Advanced Hepatocellular Carcinoma (HCC) Patients Treated With the Combination of Sorafenib Plus Nivolumab as First-Line of Systemic Therapy

TypeinterventionalSponsorRobin Kate KelleyRan2018 to 2023Enrolled16ConditionsStage III Hepatocellular Carcinoma AJCC v8, Stage IIIA Hepatocellular Carcinoma AJCC v8, Stage IIIB Hepatocellular Carcinoma AJCC v7, Stage IIIC Hepatocellular Carcinoma AJCC v7ArmsNivolumab, Sorafenib
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Bridget P KeenanHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, USA; Division of Hematology/Oncology, UCSF, San Francisco, CA, USA; Cancer Immunotherapy Program, UCSF, San Francisco, CA, USA. Electronic address: bridget.keenan@ucsf.edu.
Zenghua FanHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, USA; Division of Hematology/Oncology, UCSF, San Francisco, CA, USA; Cancer Immunotherapy Program, UCSF, San Francisco, CA, USA.
Bryan Khuong LeHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Quincy HarrisHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Jocelin ChenHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Matthew ClarkHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, USA; Division of Hematology/Oncology, UCSF, San Francisco, CA, USA; Cancer Immunotherapy Program, UCSF, San Francisco, CA, USA.
Averey LeaHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, USA; Division of Hematology/Oncology, UCSF, San Francisco, CA, USA; Cancer Immunotherapy Program, UCSF, San Francisco, CA, USA.
Li ZhangHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, USA; Division of Hematology/Oncology, UCSF, San Francisco, CA, USA; Cancer Immunotherapy Program, UCSF, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, UCSF, San Francisco, CA, USA.
Alexander CheungHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, USA; Division of Hematology/Oncology, UCSF, San Francisco, CA, USA; Cancer Immunotherapy Program, UCSF, San Francisco, CA, USA.
Frances LaraUC Davis Comprehensive Cancer Center, Sacramento, CA, USA.
John D GordanHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, USA; Division of Hematology/Oncology, UCSF, San Francisco, CA, USA.
Paige BracciHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, USA; Department of Epidemiology and Biostatistics, UCSF, San Francisco, CA, USA.
Spencer C BehrHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, USA; Department of Radiology & Biomedical Imaging, UCSF, San Francisco, CA, USA.
Lawrence FongHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, USA; Division of Hematology/Oncology, UCSF, San Francisco, CA, USA; Cancer Immunotherapy Program, UCSF, San Francisco, CA, USA; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Alan P VenookHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, USA; Division of Hematology/Oncology, UCSF, San Francisco, CA, USA.
Edward J KimUC Davis Comprehensive Cancer Center, Sacramento, CA, USA.
Robin K KelleyHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, CA, USA; Division of Hematology/Oncology, UCSF, San Francisco, CA, USA. Electronic address: katie.kelley@ucsf.edu.

Funding

Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI KC KENT LLOYD · 2002 to 2026
$84.9M
Determinants of response to cancer immunotherapyR35CA253175 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Lawrence Fong · 2021 to 2026
$5.8M
NCI NIH HHS P30 CA093373NCI NIH HHS R35 CA253175
6 · The paper itself

Abstract

BACKGROUND &

aimsImmune checkpoint inhibition (ICI) and anti-angiogenic therapies are active in hepatocellular carcinoma (HCC), although patients with impaired hepatic function have worse outcomes.

methodsWe conducted an open-label phase II clinical trial to assess the safety and efficacy of the multikinase inhibitor, sorafenib, combined with nivolumab, in patients with advanced HCC and varying liver function. In a Part 1 safety lead-in, we investigated the maximum-tolerated dose (MTD) of the combination in patients with Child-Pugh A or B7. In Part 2, we enrolled patients with Child-Pugh B7-9 HCC with the primary endpoint of grade ≥3 treatment-related adverse event (TRAE) incidence. Exploratory endpoints included immunological biomarkers.

resultsOverall, 25 patients were consented and 16 eligible patients enrolled. In Part 1, dose-limiting toxicity occurred in one of six patients in Dose Level -1, and two of five patients in Dose Level 1; Dose Level -1 was determined to be the MTD. In total, 69% of patients experienced a grade ≥3 TRAE, with similar distribution for patients with Child-Pugh A and B (70%, 95% CI: 0.35-0.93 vs. 66.7%, 95% CI: 0.22-0.96). The objective response rate was 6% and median overall survival was 12.99 months (Child-Pugh A: 15.26 and Child-Pugh B: 10.41). We found that patients with Child-Pugh B liver disease harbored more circulating suppressive CD14

conclusionsAlthough combination sorafenib and nivolumab demonstrated acceptable safety at the MTD in both Child-Pugh subgroups, the objective response rate was below the prespecified threshold to be declared worthy of further exploration. A distinct immune cell profile in patients with Child-Pugh B disease might define mechanisms of resistance and potential therapeutic targets in this population with unmet clinical need. IMPACT AND IMPLICATIONS: This study addresses the crucial need for effective therapies for patients with advanced HCC and compromised liver function, a population historically excluded from many clinical trials. The findings suggest that, although the combination of sorafenib and nivolumab demonstrated acceptable safety across different liver function subgroups, there was a low response rate overall. Importantly, the discovery of distinct immune profiles, particularly an increase in suppressive immune cells in patients with worse liver function, provides insights into potential mechanisms of resistance to immunotherapy. These results are crucial for understanding how we can improve the treatment of advanced HCC, especially in patients with impaired liver function. CLINICAL TRIAL: NCT03439891.

Indexed as

Child-Pugh scoreCirrhosisHepatocellular carcinomaImmunotherapyMonocytes

Identifiers

PMID41831609
PMCPMC13101793

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.