April 2026 marked an important period of progress in hepatobiliary cancers, with advances spanning clinical trials, real-world evidence, translational research, and emerging therapeutic strategies across hepatocellular carcinoma and biliary tract malignancies.
Key developments included new data from studies such as EMERALD-3 and COMPANION-002, further refining the role of combination approaches in both locoregional and advanced settings. At the same time, ongoing trials like MONTBLANC continue to explore novel triple immunotherapy strategies, while targeted approaches—including FGFR2 inhibition and RAS-directed therapies—highlight both progress and ongoing challenges in biomarker-driven treatment.
In parallel, real-world and comparative analyses provide additional insight into treatment decision-making, particularly in complex settings such as portal vein tumour thrombus and intermediate-stage disease, as well as the positioning of TARE versus TACE. Emerging data on treatment timing and peri-procedural immunotherapy further emphasise the importance of optimising therapeutic strategies beyond drug selection alone.
This article highlights 10 key updates from April 2026 that are shaping the current and future landscape of hepatobiliary cancer management.
NIVOLEP Trial: Peri-procedural Nivolumab + Irreversible Electroporation in Early HCC
Published on April 8, 2026, in Hepatology, Nahon et al. reported results from the phase II NIVOLEP trial, evaluating neoadjuvant and adjuvant nivolumab in combination with irreversible electroporation (IRE) in patients with early hepatocellular carcinoma at high risk of recurrence.
Study Design
NIVOLEP is a multicenter phase II trial including patients with BCLC A HCC treated with 2 neoadjuvant nivolumab infusions, curative-intent IRE, followed by 12 monthly adjuvant nivolumab infusions. The primary endpoint was 1-year local recurrence-free survival (LRFS).
Key Findings
- 43 patients included (62 HCC nodules; mean size 30 mm)
- 35 patients underwent curative-intent IRE
- Radiological response after neoadjuvant nivolumab: 24.2% (per nodules)
- Pathological response: 26.3% (per nodules)
- 1-year LRFS: 70.6% (95% CI 55.3–85.9) (primary endpoint, ITT)
- 2-year overall survival: 74.2% (ITT)
- Grade 3–4 adverse events related to nivolumab: 2 patients
- 1 treatment-related death reported
Tumour analyses showed immune activation with enrichment of T-cell, CD8+ T-cell, and B-cell infiltration
Takeaway
Peri-procedural nivolumab combined with IRE demonstrated anti-tumour activity, immune activation, and encouraging local control in early HCC, supporting further evaluation of immunotherapy in curative-intent settings.
MONTBLANC Trial: Triple Immunotherapy Strategy in Unresectable HCC
The MONTBLANC trial, evaluating durvalumab, tremelimumab, and bevacizumab in unresectable hepatocellular carcinoma, has now completed patient recruitment, marking an important milestone in the development of triple immunotherapy strategies for advanced HCC.
Study Design
MONTBLANC is a randomized, open-label, phase II clinical trial (NCT05844046) evaluating two treatment strategies in patients with unresectable HCC eligible for systemic treatment: upfront triple therapy with durvalumab, tremelimumab, and bevacizumab, versus a sequential approach starting with durvalumab plus tremelimumab, with bevacizumab added upon disease progression or insufficient radiologic response. The primary endpoint is objective response rate (ORR), with secondary endpoints including overall survival (OS), progression-free survival (PFS), safety, and patient-reported outcomes. ( Ben Khaled et al. 2026)
Recruitment Status
- Patient recruitment has been successfully completed
- Study population is fully accrued, allowing for robust evaluation of the predefined endpoints
- No efficacy or survival data have been reported, as the trial is ongoing
- Patients continue to be followed for response and long-term outcomes
- The focus now shifts toward data maturation, analysis, and eventual reporting of results
Takeaway
Completion of enrollment represents a key milestone for the MONTBLANC trial, which is now entering the follow-up phase, with results expected to clarify the role of triple immunotherapy in unresectable HCC.
Read more about MONTBLANC Trial on OncoDaily.
RAS-GTP Inhibition in KRAS-Mutant Cholangiocarcinoma
Published online on April 23, 2026, in Cancer Cell, Entrialgo-Cadierno et al. reported preclinical and early clinical findings on RAS(ON) multi-selective inhibition in KRAS-mutant cholangiocarcinoma.
Study Overview
The study evaluated RAS(ON) multi-selective inhibitors — the preclinical tool compound RMC-7977 and the investigational agent daraxonrasib (RMC-6236) — across cholangiocarcinoma cell lines, patient-derived xenografts, immunocompetent allograft models, and selected clinical cases of patients with advanced KRAS-mutant cholangiocarcinoma enrolled in the first-in-human RMC-6236-001 trial (NCT05379985).
Key Results
- About 25% of cholangiocarcinoma tumours harbor KRAS mutations
- RAS(ON) inhibition showed strong antitumour activity in cell-line, patient-derived xenograft, and immunocompetent allograft models
- RAS-GTP inhibition potentiated standard-of-care cholangiocarcinoma regimens in preclinical models
- Resistance was mainly associated with mechanisms driving RAS signalling overactivation, including SHP2 hyperactivation, KRAS amplification, and MYC overexpression
- Combining RAS-GTP inhibition with SHP2 inhibition overcame both intrinsic and acquired resistance in preclinical models
- Two patients with advanced KRAS G12-mutant cholangiocarcinoma (one G12V, one G12A) achieved confirmed partial responses on daraxonrasib monotherapy
Takeaway
RAS-GTP inhibition showed strong preclinical activity and early clinical signals in KRAS-mutant cholangiocarcinoma, supporting further clinical evaluation of this strategy, potentially in combination with SHP2 inhibition or standard chemotherapy.
COMPANION-002: Tovecimig + Paclitaxel in Second-Line Biliary Tract Cancer
Reported on April 27, 2026, Compass Therapeutics announced results from the randomized phase 2/3 COMPANION-002 trial, evaluating tovecimig plus paclitaxel versus paclitaxel alone in patients with unresectable, advanced, metastatic, or recurrent biliary tract cancer in the second-line setting.
Study Design
COMPANION-002 is a randomized, controlled phase 2/3 study (n=168) comparing tovecimig, a DLL4 × VEGF-A bispecific antibody, in combination with paclitaxel versus paclitaxel alone. Patients were randomized 2:1 (tovecimig + paclitaxel n=111, paclitaxel n=57), with crossover to tovecimig allowed upon centrally confirmed progression. The primary endpoint was overall response rate (ORR), with secondary endpoints including progression-free survival (PFS) and overall survival (OS).
Key Findings
- ORR: 17.1% with tovecimig + paclitaxel vs 5.3% with paclitaxel alone (p=0.031)
- Median PFS: 4.7 vs 2.6 months (HR 0.44; p<0.0001)
- Median OS in the ITT analysis: 8.9 vs 9.4 months (HR 1.05; p=0.78), with 54% of control patients crossing over to tovecimig
- Among patients randomized to paclitaxel alone, crossover patients had median OS 12.8 months vs 6.1 months in non-crossover patients (HR 0.54; p=0.04)
- PFS2 (post-crossover) in the same patients: 3.5 vs 1.9 months (HR 0.36; p=0.0016)
- Pooled OS for all tovecimig-exposed patients (85% of the study): 8.9 months
- Safety profile consistent with prior studies, with no new safety signals
Takeaway
Tovecimig plus paclitaxel improved response rates and progression-free survival in second-line biliary tract cancer, with overall survival analyses confounded by extensive crossover, supporting further development of this bispecific antibody strategy.
Read more about COMPANION-002 on OncoDaily.
TARE vs TACE in Early–Intermediate HCC: Systematic Review and Meta-analysis
Published on April 28, 2026, in World Journal of Surgical Oncology, Mirza et al. reported a systematic review and meta-analysis comparing transarterial radioembolization (TARE) versus transarterial chemoembolization (TACE) in early- to intermediate-stage unresectable hepatocellular carcinoma.
Study Overview
This meta-analysis included randomized controlled trials comparing Yttrium-90 TARE versus TACE, evaluating survival, tumour response, safety, and downstaging outcomes.
Key Findings
- 4 RCTs included (n=169; TARE n=87, TACE n=82)
- No significant differences between TARE and TACE in PFS (HR 0.72), OS (HR 0.82), ORR (OR 1.32), or downstaging to transplantation (OR 2.19)
- TARE associated with fewer treatment-related adverse events (OR 0.38; p=0.005)
- Quality of life outcomes were comparable between groups
Takeaway
TARE and TACE demonstrated similar efficacy outcomes, with TARE showing a more favourable safety profile in early- to intermediate-stage HCC.
PROOF 301: Infigratinib vs Gemcitabine–Cisplatin in FGFR2-Rearranged Cholangiocarcinoma
Published in April 2026, in ESMO Open, Abou-Alfa et al. reported results from the phase III PROOF 301 trial, evaluating infigratinib versus gemcitabine plus cisplatin in previously untreated patients with advanced cholangiocarcinoma harboring FGFR2 fusions or rearrangements.
Study Design
PROOF 301 is a randomized, open-label, phase III study comparing oral infigratinib (125 mg on days 1–21 of a 28-day cycle) versus gemcitabine plus cisplatin in the first-line setting. Patients were randomized 2:1, with a target accrual of approximately 300 patients. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review. The study was terminated early due to poor accrual.
Key Findings
- 1127 patients pre-screened across 120 sites; 48 randomized (29 to infigratinib, 19 to chemotherapy)
- Median PFS (BICR): 7.4 months with infigratinib vs 8.0 months with chemotherapy
- ORR (BICR): 37.9% vs 15.8%
- Disease control rate: 86.2% vs 73.7%
- Median overall survival: not estimable in both arms
- Grade 3–4 adverse events: 79.3% vs 58.8%
Takeaway
Early termination of PROOF 301 limited definitive conclusions on efficacy, highlighting the challenges of conducting randomized trials in biomarker-selected populations of rare cancers such as FGFR2-rearranged cholangiocarcinoma.
Read more about PROOF 301 on OncoDaily.
Liver Resection vs TACE + Immunotherapy in HCC with PVTT
Published on March 23, 2026, in BJS Open, Guo et al. reported a multicentre retrospective study comparing liver resection versus transarterial chemoembolization (TACE), both combined with PD-1 inhibitors and lenvatinib, in patients with hepatocellular carcinoma and portal vein tumour thrombus (PVTT).
Study Design
The study included 430 patients treated between 2019 and 2023 across seven Chinese tertiary hospitals. After 1:1 propensity score matching, 155 patients were analysed in each group: liver resection plus PD-1 inhibitors and lenvatinib (LRPL) versus TACE plus the same systemic therapy (TPL). The primary endpoint was overall survival.
Key Findings
- Median OS: 34.0 months with LRPL vs 22.9 months with TPL (HR 0.71; 95% CI 0.53–0.95; p = 0.022)
- Survival benefit was driven by patients with Vp1–2 PVTT (HR 0.36; 95% CI 0.21–0.64; p < 0.001)
- No OS difference was observed in Vp3–4 disease (HR 0.98; 95% CI 0.68–1.41; p = 0.910); interaction p = 0.004
- In the TPL group, ORR reached 51.7% (RECIST) and 57.1% (mRECIST), with DCR above 80%
- Conversion to resection was achieved in 19% of patients in the TPL cohort
Takeaway
These data suggest that a surgery-based strategy combined with immunotherapy and lenvatinib may offer a survival advantage in selected patients with PVTT, particularly when thrombus involvement is limited to segmental or second-order branches.
Metabolomic Profiling of Gefitinib in Hepatocellular Carcinoma
Published on April 29, 2026, in Biomedical Chromatography, Li et al. investigated the metabolic effects of gefitinib in hepatocellular carcinoma using GC/MS- and LC/MS-based metabolomic profiling.
Study Overview
Untargeted metabolomic analysis was performed using GC–MS and LC–MS (HILIC and reversed-phase) platforms, with six samples per group. The study was motivated by recent findings suggesting gefitinib, an EGFR inhibitor, may help overcome lenvatinib resistance in HCC.
Key Results
- A total of 42 metabolites were identified, with 25 showing significant changes after gefitinib treatment (p < 0.05)
- Metabolic profiles clearly separated between groups on PCA and OPLS-DA analysis
- Pathway enrichment revealed alterations in four key pathways: arginine–proline metabolism, nitrogen metabolism, branched-chain amino acid biosynthesis, and taurine metabolism
Takeaway
Metabolomic analysis identified pathway-level alterations associated with gefitinib treatment in hepatocellular carcinoma, providing a foundation for understanding the metabolic mechanisms behind its potential to overcome therapy resistance.
EMERALD-3: STRIDE + Lenvatinib + TACE in Unresectable HCC
Reported on April 2, 2026, AstraZeneca announced results from the phase III EMERALD-3 trial, evaluating durvalumab (Imfinzi) plus tremelimumab (Imjudo) in combination with lenvatinib and transarterial chemoembolisation (TACE) in patients with unresectable hepatocellular carcinoma eligible for embolisation.
Study Design
EMERALD-3 is a randomized, open-label, sponsor-blinded, multicentre, global phase III trial enrolling 760 patients with unresectable HCC eligible for embolisation, conducted across 171 centres in 22 countries. Patients were randomized between three arms: STRIDE (durvalumab plus tremelimumab) + lenvatinib + TACE, STRIDE + TACE, or TACE alone. The primary endpoint is progression-free survival (PFS) for the quadruplet regimen vs TACE alone, with overall survival (OS) as a key secondary endpoint.
Key Findings
- Statistically significant and clinically meaningful improvement in PFS with STRIDE + lenvatinib + TACE vs TACE alone
- OS analysis at interim showed a trend toward improvement vs TACE alone
- STRIDE + TACE (without lenvatinib) also showed strong trends toward improved PFS and OS, though not formally tested
- Safety profile consistent with known profiles of each agent, with no new safety signals
- Detailed numerical data have not yet been released; full results to be presented at an upcoming medical meeting
Takeaway
The EMERALD-3 trial demonstrates that adding STRIDE-based immunotherapy with lenvatinib to TACE improves progression-free survival in embolisation-eligible unresectable HCC, with overall survival data still maturing.
Read more about EMERALD-3 Trial on OncoDaily.
Timing of First Immunotherapy Dose and Outcomes in HCC
Published on April 21, 2026, in Journal for ImmunoTherapy of Cancer, Li et al. reported a retrospective study evaluating whether the timing of the first immune checkpoint inhibitor (ICI) infusion influences outcomes in patients with advanced hepatocellular carcinoma.
Study Overview
The study included 84 patients treated with ICIs, grouped based on timing of the first infusion: morning (before 12:00) versus afternoon (after 12:00). Clinical outcomes and immune profiles were analysed.
Key Results
- Median PFS: 4.7 months in the morning group vs 2.8 months in the afternoon group
- Morning infusion associated with improved PFS (HR 0.50; 95% CI 0.30–0.84; p < 0.01)
- Higher odds of objective response in the morning group (OR 3.26; p < 0.05)
- Overall survival was numerically longer in the morning group but not statistically significant
- Timing of subsequent infusions had no impact on outcomes
- No increase in immune-related adverse events with morning dosing
- Lower IL-6 levels and increased expansion of cytotoxic central memory CD8+ T cells observed in the morning group
Takeaway
Morning administration of the first ICI dose was associated with improved progression-free survival and response, with corresponding differences in immune activation, suggesting that timing of treatment initiation may influence immunotherapy outcomes.
Find out Top 10 Gastroesophageal Cancer Updates – March 2026 on OncoDaily.