Hepatocellular Carcinoma
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Jul 13 – Jul 20, 2026
PD-1 blockade unleashes local hepatitis B virus-related B cell response inhibiting hepatocellular carcinoma.
CANCER CELL · Q1 JOURNAL - RANK #5/326TOP-TIER
This study investigated the mechanisms of anti-PD-1 therapy in a phase 2 clinical trial (NCT04615143) involving patients with resectable recurrent hepatocellular carcinoma (HCC). Using single-cell multi-omics, clonal antibody repertoire analysis, and spatially paired scRNA-seq/BCR-seq, the study identified a distinct B cell–driven immune subtype marked by somatic hypermutation and antibody responses targeting hepatitis B virus antigens within tumor tertiary lymphoid structures. Mechanistically, these antibodies activate a complement-mediated antitumor response, augmenting anti-PD-1 efficacy. The findings reveal enhanced antiviral B cell immunity as a mechanism of action in anti-PD-1-treated HCC patients, with preclinical validation in mouse models demonstrating improved therapeutic outcomes.
10.1016/j.ccell.2026.06.010
GPC3-specific dnTGFβRII-armoured CAR T cells for hepatocellular carcinoma.
NATURE · Q1 JOURNAL - RANK #2/135TOP-TIER
This first-in-human, dose-escalation clinical trial (NCT05155189) evaluated GPC3-directed CAR T cells incorporating a dominant-negative TGFβ receptor II (C-CAR031) in adults with advanced, treatment-refractory hepatocellular carcinoma. Thirty-six participants received a single infusion at four escalating doses (0.75×106–4.0×106 cells /kg) and were followed prospectively for safety, tumour response, and survival. Cytokine-release syndrome occurred in 34/36 patients (grade 3 in 2), with nine grade ≥3 non-haematological adverse events; tumour regression was seen in 32 patients, giving an objective response rate of 44.4 %, median best tumour reduction of 41.6 %, median response duration of 4.4 months, progression-free survival of 4.2 months, and overall survival of 14.2 months. The study concludes that C-CAR031 is tolerable and shows encouraging antitumour activity, though resistance mechanisms may involve GPC3 loss and elevated TGFβ.
10.1038/s41586-026-10786-z
Jul 06 – Jul 13, 2026
Selective Conventional Transarterial Chemoembolization Using a Glass Membrane Emulsification Device in Hepatocellular Carcinoma: Multicenter Clinical Trial in Japan.
LIVER CANCER · Q1 JOURNAL - RANK #11/147
This multicenter phase II trial (jRCTs052200095) evaluated selective conventional transarterial chemoembolization (cTACE) using a porous glass membrane emulsification device in 50 patients with unresectable hepatocellular carcinoma (≤5 cm; Child-Pugh A or B). The emulsion of epirubicin and ethiodized oil was injected into tumor-feeding arteries, followed by gelatin sponge embolization, with the primary endpoint being complete response (CR) rate at 3 months. Among 45 patients in the efficacy analysis, the CR rate at both 1 and 3 months was 97.8% (95% CI: 88.2-99.9%), with serious adverse events including elevated AST (50.0%) and ALT (29.2%). The study concluded that this cTACE technique achieved high short-term CR rates with acceptable safety, supporting further investigation.
10.1159/000552424
Long-term follow-up of a phase 1/2 trial of anti-GDF-15 antibody visugromab plus anti-PD-1 antibody nivolumab in anti-PD-1/-L1 relapsed/refractory solid tumors.
J HEMATOL ONCOL · Q1 JOURNAL - RANK #1/98TOP-TIER
This multicenter phase 1/2a clinical trial evaluated visugromab, an anti-GDF-15 antibody, plus nivolumab in 77 patients with anti-PD-1/PD-L1-relapsed/refractory locally advanced/metastatic non-squamous NSCLC, urothelial carcinoma, or hepatocellular carcinoma. Patients received both drugs every two weeks until progression or unacceptable toxicity, and responses were assessed via RECIST v1.1. Objective response rates were 18.2% (NSCLC), 18.5% (UC), and 14.3% (HCC), with median duration of response ranging from 19.4 to 32.2 months and 53.8% of responses ongoing; 61.5% achieved confirmed complete or metabolic response. The study concludes that GDF-15 blockade with visugromab enhances response rates and durability versus prior anti-PD-1/PD-L1 therapy, suggesting its value for further randomized investigation.
10.1186/s13045-026-01818-2
Jun 29 – Jul 06, 2026
Neoadjuvant Danburstotug (IMC-001) therapy in gastric, esophageal, and hepatocellular carcinoma: the NeoChance phase II study.
NPJ PRECIS ONCOL · Q1 JOURNAL - RANK #39/326
This phase II trial evaluated neoadjuvant danburstotug (20 mg/kg every 2 weeks) in resectable gastric cancer, esophageal squamous cell carcinoma, and hepatocellular carcinoma patients. Forty-eight patients received two cycles before surgery, with the primary endpoint of major pathologic response (MPR, <10% viable tumor). MPR was achieved in 2/48 patients (4.2%), failing the pre-specified endpoint, though pathologic regression ≤50% occurred in 22.9% of patients. The treatment was safe with only 6.0% grade ≥3 adverse events and no grade 4-5 events, and all patients underwent R0 resection.
10.1038/s41698-026-01571-2
Perioperative tislelizumab for early-stage hepatocellular carcinoma: A phase II trial with integrated tumour microenvironment profiling and predictive modeling.
DRUG RESIST UPDATE · Q1 JOURNAL - RANK #2/352TOP-TIER
This prospective, single-arm, phase II trial investigated neoadjuvant tislelizumab monotherapy with adaptive escalation to tislelizumab + lenvatinib in 36 patients with resectable early-stage hepatocellular carcinoma, accompanied by tumour-microenvironment profiling and biomarker modelling. All participants received two cycles of tislelizumab; non-responders received additional lenvatinib before surgery, and 33 proceeded to resection. Objective response rates were 13.9 % by RECIST v1.1 and 30.6 % by mRECIST; major pathological response and complete pathological response were observed in 33.3 % and 15.2 % of resected patients, respectively, while grade ≥3 treatment-emergent adverse events occurred in 11.1 % without delaying surgery. Immune-regulatory CAF-T-cell colocalization and a multimodal blood-imaging model (average precision 0.9167, 100 % specificity) accurately identified responders, supporting the safety and antitumour activity of perioperative tislelizumab and the feasibility of biomarker-guided patient selection.
10.1016/j.drup.2026.101440
Liver tumor motion and reconstructed doses in a clinical trial of respiratory gated proton therapy for hepatocellular carcinoma.
INT J RADIAT ONCOL · Q1 JOURNAL - RANK #14/212
In a prospective phase II trial, 16 patients with HCC received 58-67.5 Gy (RBE) of respiratory-gated pencil beam scanning proton therapy in 15 fractions to evaluate tumor motion and actual delivered dose. Gating was performed using an external gating block, with CBCT-guided fiducials measuring mean (±SD) root-mean-square tumor position error of 1.1±0.8 mm (L-R), 2.9±1.2 mm (C-C), and 1.6±0.7 mm (A-P). Evaluated via weekly 4DCT dose recalculations, motion increased CTV homogeneity index ((D2%-D98%)/D50%) by 4.1±2.6 percentage points for individual fractions, but only 1.5±2.1 points overall. The study concludes that while intrafraction motion creates interplay effects on single fractions, target dose coverage remains robust over multiple fractions.
10.1016/j.ijrobp.2026.06.3073
Camrelizumab, a patinib and radiotherapy in locally advanced, unresectable hepatocellular carcinoma: a phase 2 study.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This single-arm, phase 2 trial investigated the combination of camrelizumab, apatinib, and intensity-modulated radiotherapy in locally advanced, unresectable HCC. A total of 44 patients (90.9% with BCLC stage C) were enrolled and received camrelizumab (200 mg IV every 3 weeks), apatinib (250 mg daily), and 50–60 Gy of radiotherapy for up to two years. The objective response rate was 84.1%, median progression-free survival was 13.8 months, and median overall survival was not reached (24-month PFS and OS rates were 38.1% and 70.2%, respectively). Camrelizumab and apatinib combined with radiotherapy demonstrated promising efficacy and manageable toxicity, supporting further investigation in randomized trials.
10.1158/1078-0432.CCR-26-1352
Intratumoral bicarbonate functions as an adjuvant to potentiate PD-1 blockade in hepatocellular carcinoma.
ONCOGENE · Q1 JOURNAL - RANK #16/191
The study investigated whether intratumoral alkalization with sodium bicarbonate could enhance PD-1 blockade in hepatocellular carcinoma (HCC). A prospective clinical trial (ChiCTR2100053537) enrolled 30 patients (28 advanced-stage, 2 intermediate-stage HCC) who received Tislelizumab plus intratumoral 5% sodium bicarbonate, yielding an objective response rate of 93.3% (CR 53.3%, PR 40.0%) and median progression-free survival of 31 months. Biopsies showed increased CD3⁺, CD4⁺, and CD8⁺ T-cell infiltration with combination therapy versus Tislelizumab alone. The findings suggest intratumoral bicarbonate is a safe and effective adjuvant that significantly enhances PD-1 blockade efficacy in HCC.
10.1038/s41388-026-03836-3
Jun 22 – Jun 29, 2026
Nivolumab plus Ipilimumab versus Lenvatinib or Sorafenib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: CheckMate 9DW Japanese Subgroup Analysis.
LIVER CANCER · Q1 JOURNAL - RANK #11/147
This preplanned interim analysis of the phase 3, randomized, open-label CheckMate 9DW trial assessed nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) versus investigator-choice lenvatinib or sorafenib as first-line therapy in 56 Japanese patients with unresectable hepatocellular carcinoma. Patients were randomized 1:1 and followed for a median of 35.8 months; overall survival (primary endpoint) and objective response rate/duration of response by blinded independent central review were measured, with safety as an exploratory endpoint. Median overall survival was not reached with nivolumab + ipilimumab versus 32.0 months with lenvatinib/sorafenib (HR 0.64, 95% CI 0.27–1.50), and ORR was 56% versus 16%, respectively, while grade 3/4 treatment-related adverse events occurred in 50% and 65% of patients. The authors conclude that nivolumab plus ipilimumab provides clinically meaningful survival and response benefits with manageable toxicity, supporting its use as a new first-line option for Japanese patients with unresectable HCC.
10.1159/000548300
ALBI Grade is a Determinant of Lenvatinib Pharmacokinetics, Efficacy, and Toxicities in Japanese Patients with Hepatocellular Carcinoma.
CLIN PHARMACOKINET · Q1 JOURNAL - RANK #82/352
This prospective study enrolled 41 Japanese patients with hepatocellular carcinoma (HCC) receiving lenvatinib to examine the effects of baseline albumin-bilirubin (ALBI) grade on unbound lenvatinib pharmacokinetics, efficacy, and toxicity. Key methodology included measurement of total- and unbound-base dose-normalized area under the plasma concentration-time curve (AUCt/dose and AUCu/dose), progression-free survival (PFS), and toxicities. AUCu/dose was significantly negatively correlated with ALBI score (P=0.00699), and ALBI grade ≥2b was associated with higher AUCu/dose, shorter PFS (HR 9.43, 95% CI 3.18-28.0, P=0.0000521), and increased toxicity (87.0% vs 55.6%, P=0.0357). The study concludes that baseline ALBI grade is a determinant of lenvatinib pharmacokinetics and clinical outcomes in HCC.
10.1007/s40262-026-01662-0
Efficacy of hydrocolloid dressing for hand-foot skin reaction: J-SUPPORT 1701 APRON trial.
SUPPORT CARE CANCER · Q1 JOURNAL - RANK #17/173
This phase 3 randomized self-controlled study evaluated the efficacy of hydrocolloid dressing versus standard prophylactic moisturizing alone in preventing hand-foot skin reaction (HFSR) among 50 patients with unresectable colorectal cancer, gastrointestinal stromal tumors, or hepatocellular carcinoma receiving regorafenib or sorafenib. The primary endpoint was incidence of grade 2 or higher HFSR, assessed with blinded central review and patient-reported outcomes. Results showed a significantly lower rate of grade 2 or higher HFSR in the hydrocolloid group versus control (20% vs. 50%, p < 0.0001; HR for time to event 0.32, p = 0.0017) and reduced patient-reported moderate to severe HFSR (10% vs. 32%, p = 0.0002). The authors concluded that hydrocolloid dressings provide effective prophylaxis for HFSR in this population.
10.1007/s00520-026-10902-9
Addition of ipilimumab to atezolizumab plus bevacizumab in advanced hepatocellular carcinoma (PRODIGE 81-FFCD 2101-TRIPLET HCC): phase 2 results from a randomised, multicentre, open-label, phase 2-3 trial.
LANCET GASTROENTEROL · Q1 JOURNAL - RANK #2/147TOP-TIER
This phase 2-3 trial (PRODIGE 81-FFCD 2101-TRIPLET HCC) is a prospective, randomised, multicentre, open-label human clinical trial evaluating the addition of ipilimumab to atezolizumab plus bevacizumab in 226 patients with unresectable hepatocellular carcinoma. Patients were randomly assigned 1:1 to triple therapy or doublet therapy, with a primary endpoint of objective response within 24 weeks per RECIST v1.1. At 24 weeks, 30% (80% CI 24-36) of the triple therapy group achieved an objective response versus 27% (22-34) in the doublet group, falling short of the prespecified threshold of 35 responses; the trial was stopped. The authors conclude the triple combination provides no benefit and does not support its use in first-line treatment.
10.1016/S2468-1253(26)00115-9
Jun 08 – Jun 15, 2026
Nivolumab in combination with lenvatinib in unresectable hepatocellular carcinoma: The IKF-t006/IMMUNIB translational phase-2 study.
EUR J CANCER · Q1 JOURNAL - RANK #45/326
This single-arm, phase-2 clinical trial evaluated the efficacy of nivolumab in combination with lenvatinib as first-line therapy for unresectable hepatocellular carcinoma (HCC). Fifty patients were enrolled, with 49 receiving treatment, yielding a primary endpoint of objective response rate (ORR) at 32% (95% CI: 19.5–46.7), below the prespecified threshold of 43%. Median progression-free survival (PFS) was 9.0 months, median overall survival (OS) was 26.6 months, and Grade ≥3 adverse events included colitis, diarrhea, hypertension, and elevated bilirubin. The study demonstrated durable clinical activity and prolonged survival in a subset of patients, supporting further investigation of tyrosine kinase inhibitor/immune checkpoint inhibitor combinations and biomarker-driven therapies in HCC.
10.1016/j.ejca.2026.116847
A phase Ib/2a study of fostrox in combination with lenvatinib as second line therapy in patients with advanced hepatocellular carcinoma.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This multicentre, single-arm Phase Ib/2a trial evaluated fostrox plus lenvatinib for advanced HCC after prior therapies. In this 3+3 dose escalation study, fostrox was administered orally for five days in 21-day cycles with lenvatinib at standard doses to 21 patients. Dose-limiting toxicities were not observed, the recommended Phase 2 dose was 30 mg, and efficacy results included an ORR of 24%, DCR of 81%, median TTP of 10.9 months, median PFS of 6.7 months, and median OS of 13.7 months. These findings suggest that fostrox plus lenvatinib is safe and effective, warranting further clinical investigation as a second-line option in advanced HCC.
10.1158/1078-0432.CCR-26-0273
Hepatic Arterial Infusion Chemotherapy plus either Toripalimab or Sorafenib as First-line Therapy for Locally Advanced Hepatocellular Carcinoma: A Non-comparative, Randomized Phase 2 Trial.
MEDCOMM · Q1 JOURNAL - RANK #14/195TOP-TIER
This single-center, non-comparative, randomized phase II trial (NCT04135690) evaluated hepatic arterial infusion chemotherapy (HAIC) plus toripalimab versus HAIC plus sorafenib as first-line therapy for locally advanced hepatocellular carcinoma. Seventy-two patients were randomized 1:1 to TorHAIC or SoraHAIC every 3 weeks, with the primary endpoint of 6-month progression-free survival (PFS) rate. The 6-month PFS rate was 63.9% for TorHAIC and 61.1% for SoraHAIC; median PFS was 9.1 vs 7.2 months and median overall survival was 20.9 vs 16.4 months. Grade 3–4 adverse events occurred in 33.3% vs 44.4% and serious AEs in 2 vs 5 patients, suggesting TorHAIC has favorable safety and efficacy, warranting phase III validation.
10.1002/mco2.70805
Jun 01 – Jun 08, 2026
A first-in-human, open-label multicentre Phase 1 study of the orally administered E7386 in patients with selected advanced neoplasms.
BRIT J CANCER · Q1 JOURNAL - RANK #47/326
E7386 is an oral protein–protein interaction inhibitor that blocks the CBP/β-catenin interaction, evaluated in a first-in-human Phase 1 open-label study in adults with advanced or recurrent solid tumors or CTNNB1-mutated hepatocellular carcinoma. The study aimed to assess safety and tolerability for dose escalation to determine a recommended Phase 2 dose in 38 patients receiving 5–120 mg twice daily. The most common treatment-related adverse events were nausea (65.8%) and vomiting (60.5%), stable disease was observed in 36.8% of patients, and some experienced disease control for at least 23 weeks. Overall, E7386 demonstrated an acceptable safety profile, with a dose-dependent pharmacokinetic profile and potential for disease stabilization in this heavily pretreated population.
10.1038/s41416-026-03488-w