Hepatocellular Carcinoma
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May 18 – May 25, 2026
A Multicenter Phase II Study on Atezolizumab plus Bevacizumab Combination Therapy in Patients with Unresectable Hepatocellular Carcinoma and Child-Pugh Classification B Cirrhosis: CHALLENGE Trial.
LIVER CANCER · Q1 JOURNAL - RANK #11/147
This multicenter, open-label, single-arm phase II study assessed the safety and efficacy of atezolizumab (1,200 mg) plus bevacizumab (15 mg/kg) in 30 patients with unresectable hepatocellular carcinoma (HCC) and Child-Pugh B cirrhosis (scores 7-8). The primary endpoint of serious adverse events (SAEs) revealed a frequency of 23.3% (95% CI: 9.9–42.3%; p < 0.0001), while the objective response rates were 40.0% and 46.7% based on RECIST v1.1 and modified RECIST, respectively. Median progression-free survival was 240 days (95% CI: 176–526), and median overall survival was 470 days (95% CI: 256–576). The study concluded that this combination therapy is safe, with demonstrable antitumor activity, and further studies are necessary to confirm its potential in this patient population.
10.1159/000551476
Durvalumab plus HAIC-FOLFOX followed by maintenance durvalumab for hepatocellular carcinoma with major portal invasion: phase 2 DurHope study.
NAT COMMUN · Q1 JOURNAL - RANK #10/135TOP-TIER
The DurHope study was a single-arm phase 2 clinical trial evaluating durvalumab plus HAIC-FOLFOX as first-line treatment in 30 hepatocellular carcinoma (HCC) patients with Vp3/4 portal vein tumor thrombus (PVTT). Primary endpoint was 1-year overall survival (OS) rate, which was 63.3%, with a median OS of 13.9 months (95% CI, 10.7-NR). Secondary endpoints included progression-free survival, objective response rate, and safety, with exploratory biomolecular analyses revealing immune and chemotherapy resistance signatures. The study concluded that the combination therapy showed promising efficacy and tolerable toxicity, with potential biomarkers for response.
10.1038/s41467-026-73131-y
May 11 – May 18, 2026
HILL: the efficacy and safety of hepatic arterial infusion chemotherapy with the FOLFOX regimen combined with lenvatinib and the PD-L1 inhibitor durvalumab in unresectable hepatocellular carcinoma: a prospective, single-arm, phase 2 clinical trial.
SIGNAL TRANSDUCT TAR · Q1 JOURNAL - RANK #1/319TOP-TIER
This prospective, single-arm, phase 2 clinical trial evaluated the efficacy and safety of FOLFOX-HAIC combined with lenvatinib and durvalumab as initial therapy for 40 patients with unresectable hepatocellular carcinoma. The primary endpoint was progression-free survival; secondary endpoints included objective response rate, disease control rate, overall survival, and safety. With a median follow-up of 23.1 months, median progression-free survival was 15.8 months, objective response rate was 75.0%, and 1- and 2-year overall survival rates were 97.5% and 94.0%, respectively. The authors concluded that the triple combination demonstrates promising efficacy and a tolerable safety profile, warranting further investigation.
10.1038/s41392-026-02718-0
Continuation of First-Line Systemic Therapy with Progression-Directed Radiotherapy in Patients with Oligoprogressive Hepatocellular Carcinoma: A Multicenter, Single-Arm, Phase II Trial.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This study evaluated the efficacy and safety of progression-directed radiotherapy (PDRT) in combination with ongoing first-line systemic therapy (FLST) in patients with oligoprogressive hepatocellular carcinoma (OP-HCC) in a multicenter, single-arm, phase II clinical trial. Involving 36 patients, the study reported a median progression-free survival (PFS) of 7.0 months (95% CI 4.9–9.7) and a 1-year overall survival (OS) rate of 86.4%, with an objective response rate (ORR) of 64.7% and a disease control rate (DCR) of 98.0%. Quality of life (QoL) remained stable overall despite transient increases in fatigue and pain, while grade ≥3 toxicities were observed in four patients (11.1%). The results support the feasibility and safety of maintaining FLST with PDRT for OP-HCC, and propose stratification by FLST type and baseline albumin-bilirubin (ALBI) grade to optimize PFS prediction.
10.1158/1078-0432.CCR-25-4502
A Phase 1b Study of Botensilimab and Balstilimab in Treatment-Refractory Hepatocellular Carcinoma.
LIVER CANCER · Q1 JOURNAL - RANK #11/147
This open-label, non-randomized phase 1b clinical trial assessed the safety and antitumor activity of the Fc-enhanced anti-CTLA-4 antibody botensilimab combined with the anti-PD-1 antibody balstilimab in 19 patients with advanced hepatocellular carcinoma that had progressed on prior immunotherapy. Patients received botensilimab 1 or 2 mg/kg every 6 weeks plus balstilimab 3 mg/kg every 2 weeks for up to two years; efficacy was evaluated in 18 patients with at least one post-baseline scan. The objective response rate was 17 % (3/18; 95 % CI 4–41), 18-week clinical benefit rate 50 % (9/18; 95 % CI 26–74), median progression-free survival 4.4 months (95 % CI 1.4–6.9) and median overall survival 12.3 months (95 % CI 8.4–21.4); no treatment-related deaths occurred, though 68 % experienced immune-mediated adverse events (37 % Grade 3). Authors conclude that botensilimab plus balstilimab shows durable responses and manageable toxicity in treatment-refractory HCC, warranting further randomized evaluation.
10.1159/000551630
Characterization of Patients with Unresectable Hepatocellular Carcinoma in REFLECT Who Achieved Tumor Response or Alpha-Fetoprotein Response When Treated with Lenvatinib.
LIVER CANCER · Q1 JOURNAL - RANK #11/147
This subanalysis of the phase 3 REFLECT trial evaluated outcomes in lenvatinib-treated patients with unresectable hepatocellular carcinoma based on tumor reduction and alpha-fetoprotein (AFP) response. Tumor response was categorized by maximal reduction, with durations of response ranging from 3.7 months (≥30%–<50%) to 9.1 months (≥75%), and median PFS/OS up to 11.0/23.4 months for highest reduction. AFP responders had improved efficacy, with objective response rate of 48.0% versus 13.7% in nonresponders, and median PFS/OS of 7.4/13.4 months vs. 3.5/8.3 months. The analysis demonstrates tumor reduction and AFP response predict survival, reinforcing lenvatinib’s efficacy as first-line therapy.
10.1159/000551313
May 04 – May 11, 2026
TACE plus lenvatinib and envafolimab for conversion therapy in unresectable HCC: a prospective pilot study.
FRONT IMMUNOL · Q1 JOURNAL - RANK #32/183
This prospective, single-center, open-label, single-arm pilot trial evaluated transarterial chemoembolization (TACE) plus oral lenvatinib and subcutaneous envafolimab as conversion therapy for unresectable Barcelona Clinic Liver Cancer stage B/C hepatocellular carcinoma enrolled April–September 2024. Fifteen patients received repeated TACE and systemic agents until resectability, progression, toxicity or death; primary endpoint was conversion to curative-intent resection with secondary ORR, DCR, pathological response, PFS, OS and safety. Conversion to R0 resection occurred in 9/15 patients (60.0%); mRECIST ORR and DCR were 53.3% and 86.7%, respectively, five of nine resected patients achieved complete or major pathological response, median PFS was 12.0 months, and 1-year and 18-month OS were 100% and 93.3%. Treatment-related adverse events were as expected, though gastrointestinal bleeding was notable, supporting promising efficacy but underscoring the need for larger controlled trials.
10.3389/fimmu.2026.1802197
Sintilimab and lenvatinib plus hepatic arterial infusion chemotherapy and embolization as conversion therapy for uHCC: A phase 2 trial.
MED-CAMBRIDGE · Q1 JOURNAL - RANK #11/195TOP-TIER
This single-arm prospective phase II clinical trial investigated sintilimab and lenvatinib plus TACE-HAIC as conversion therapy for unresectable hepatocellular carcinoma (uHCC) in 57 patients. The primary endpoint was conversion-to-resection rate, with 77.2% (44/57; 95% CI, 0.64-0.87) achieving resection after a median of three treatment cycles, and objective response rates of 80.7% (mRECIST) and 43.8% (RECIST 1.1). Grade ≥3 treatment-related adverse events were observed in 64.9% of cases, without treatment-related deaths; median PFS was 17.3 months post-resection, and inverse probability of treatment weighting showed longer PFS (HR = 0.55, p = 0.020) and OS (HR = 0.50, p = 0.029) compared to historical controls. The combination therapy demonstrated favorable efficacy and safety for conversion to resection in uHCC.
10.1016/j.medj.2026.101132
Sintilimab (PD-1 inhibitor) plus lenvatinib as conversion therapy followed by sequential surgery (SILENSES) for advanced unresectable hepatocellular carcinoma: a phase II, expansion trial.
SIGNAL TRANSDUCT TAR · Q1 JOURNAL - RANK #1/319TOP-TIER
This prospective, single-arm, expansion phase II trial (ChiCTR1900023914) assessed sintilimab plus lenvatinib as conversion therapy followed by optional hepatectomy in 120 patients with initially unresectable hepatocellular carcinoma. Patients received the drug combination; after imaging-confirmed response, 60 consented to surgical resection. Conversion was achieved in 56% (67/120) with objective response rates of 58.3% by mRECIST and 45.8% by RECIST v1.1. After 41.0-month median follow-up, median overall survival for the entire cohort was 36.0 months (95% CI 25.0–NE) with a 5-year OS of 42.6%, while resected patients showed a median recurrence-free survival of 40 months and 5-year survival of 73.9%; grade ≥3 treatment-related adverse events occurred in 31%.
10.1038/s41392-026-02708-2
Apr 27 – May 04, 2026
AdvanTIG-206: a phase II, randomized study of ociperlimab plus tislelizumab and BAT1706 (bevacizumab biosimilar) versus tislelizumab and BAT1706 in first-line hepatocellular carcinoma.
CANCER IMMUNOL IMMUN · Q1 JOURNAL - RANK #68/326
This phase II, multicenter, randomized, multi-arm, open-label trial evaluated ociperlimab plus tislelizumab and BAT1706 versus tislelizumab plus BAT1706 in first-line hepatocellular carcinoma (HCC). 94 patients were randomized to Arm A (n=62) and Arm B (n=32). Confirmed objective response rate (ORR) was 37.1% (95% CI: 25.2-50.3) for Arm A and 40.6% (95% CI: 23.7-59.4) for Arm B, with no improved efficacy from adding ociperlimab. Treatment-related TEAEs occurred in 90.3% (Arm A) and 80.6% (Arm B), with Grade≥3 events in 59.7% and 32.3%, respectively, indicating a manageable safety profile.
10.1007/s00262-026-04399-8
Apr 20 – Apr 27, 2026
Laparoscopic extrahepatic Glissonian versus hilar dissection approach for major hepatectomy in patients with HCC: a randomized controlled trial.
BRIT J CANCER · Q1 JOURNAL - RANK #47/326
This randomized controlled trial compared short- and long-term outcomes of the Glissonian versus hilar dissection approaches for laparoscopic major hepatectomy (LMH) in 256 patients with hepatocellular carcinoma (HCC). Of the enrolled patients, 119 were assigned to the Glissonian group, and 121 to the hilar dissection group, with outcomes analyzed using a modified intention-to-treat principle. The results showed comparable 5-year overall survival (OS) and disease-free survival (DFS) rates between the groups, while the Glissonian approach resulted in significantly shorter operative time (P=0.044) and hilar dissection time (P<0.001), and fewer complications for patients with liver cirrhosis, including less intraoperative blood loss (P=0.004). The authors concluded that the Glissonian approach demonstrates superior short-term outcomes but offers comparable survival outcomes compared to hilar dissection for selected HCC patients undergoing LMH.
10.1038/s41416-026-03458-2
Apr 13 – Apr 20, 2026
Neoadjuvant stereotactic body radiation therapy plus immune therapy favorably remodels the hepatocellular carcinoma tumor microenvironment.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
The study aimed to evaluate the safety and efficacy of neoadjuvant stereotactic body radiation therapy (SBRT) followed by atezolizumab plus bevacizumab in patients with resectable hepatocellular carcinoma (HCC) (n=8). This single-institution, single-arm pilot study (NCT04857684) assessed treatment-related adverse events (trAE) and tumor microenvironment remodeling using spatial transcriptomics. Only one patient experienced a grade 3 trAE, seven achieved R0 resection, and one had a pathologic complete response, with all resected patients relapse-free at median follow-up of 16.3 months. The study concluded that the regimen is safe and warrants further prospective clinical trials due to enhanced anti-cancer immune infiltration and radiographic response correlation.
10.1158/1078-0432.CCR-25-4779
Impact of Age on Patient-Reported Outcomes with First-Line Camrelizumab plus Rivoceranib versus Sorafenib in Adults with Unresectable Hepatocellular Carcinoma: Post Hoc Analyses of the CARES-310 Open-Label, Randomized, Phase 3 Trial.
LIVER CANCER · Q1 JOURNAL - RANK #11/147
This post hoc analysis of the prospective, open-label, randomized phase 3 CARES-310 trial aimed to compare patient-reported outcomes (PROs), survival, and safety of first-line camrelizumab-rivoceranib versus sorafenib in adults with unresectable hepatocellular carcinoma, stratified by age (<65 vs ≥65 years). Methodologically, the authors assessed health-related quality of life (HRQoL), physical and role functioning, and symptoms, along with survival endpoints and treatment-related adverse events through validated questionnaires and routine clinical evaluations. The analysis showed meaningful improvements in PRO dimensions and a survival advantage for both age groups receiving camrelizumab-rivoceranib, despite a higher incidence (≥20%) of grade ≥3 events such as hypertension and increased AST. The authors conclude that the overall benefit-risk profile favors camrelizumab-rivoceranib over sorafenib as first-line therapy for adults with unresectable HCC of any age.
10.1159/000551156
Apr 06 – Apr 13, 2026
Neoadjuvant and adjuvant nivolumab associated with irreversible electroporation in patients with BCLC a hepatocellular carcinoma and high risk of recurrence (NIVOLEP trial).
HEPATOLOGY · Q1 JOURNAL - RANK #7/147TOP-TIER
This multicenter phase 2 trial (NIVOLEP) prospectively evaluated the combination of neoadjuvant and adjuvant nivolumab immunotherapy with irreversible electroporation (IRE) ablation in patients with BCLC A hepatocellular carcinoma at high recurrence risk. The study enrolled 43 patients with 62 HCC nodules who received two neoadjuvant nivolumab infusions, curative-intent IRE, and 12 monthly adjuvant nivolumab infusions, with tumor biopsies at baseline and during IRE. Key findings included a 1-year local recurrence-free survival of 70.6% (95% CI: 55.3-85.9%), 2-year overall survival of 74.2% in intention-to-treat analysis, and pathological/radiological response rates of 26.3% and 24.2% respectively after neoadjuvant treatment, with grade 3-4 nivolumab-related adverse events in 2 patients including 1 death. The principal conclusion was that peri-procedural nivolumab in IRE-eligible patients induces pathological responses linked to immune activation and demonstrates anti-tumoral effects, with biomarker analyses showing enrichment of leukocyte migration and T-cell activation pathways associated with response.
10.1097/HEP.0000000000001764
TCOF1 in Extracellular Vesicles predicts survival in HCC patients treated with High-Dose Conformal Radiotherapy.
JHEP REP · Q1 JOURNAL - RANK #15/147
This study’s primary objective was to investigate whether EV-based protein expression could serve as a prognostic biomarker in 37 HCC patients receiving high-dose conformal radiotherapy, with plasma-derived extracellular vesicles undergo mass spectrometry-based proteomic profiling. TCOF1 was strongly associated with poor survival (HR 6.64, CI 2.24-19.69, p<0.001), and multivariate Cox regression confirmed it as an independent predictor. Kaplan-Meier analyses and external validation further supported its prognostic utility. The authors conclude that EV-TCOF1 could refine risk stratification and guide personalized treatment strategies for HCC patients undergoing radiotherapy.
10.1016/j.jhepr.2026.101853