Liver Cancer (HCC) Clinical Trials

About Liver Cancer (HCC) trials

HCC trial design begins with underlying liver function, etiology of liver disease, and the molecular features that increasingly guide IO and targeted therapy decisions. PD-L1 (CD274) status is tested but IO has become standard front-line for advanced HCC regardless of PD-L1, with atezolizumab + bevacizumab (post-IMbrave 150) and durvalumab + tremelimumab (post-HIMALAYA) as the two primary first-line standards. CTNNB1 (β-catenin) mutations in 25-35% of HCC define the "Wnt-class" subset, which has been associated with worse response to IO and gates trials testing combinations to overcome IO resistance in this subgroup. TP53 mutations in 20-30% carry adverse prognosis. TERT promoter mutations are the most common alteration in HCC (50-60%) and contribute to molecular classification; trials testing TERT-targeted approaches are emerging in earlier-phase development.

Trial design in HCC turns on liver function, treatment line, and locoregional eligibility. Front-line metastatic trials test additions to or alternatives to atezolizumab + bevacizumab and durvalumab + tremelimumab, with new IO combinations and IO + TKI strategies. Second-line trials test cabozantinib, ramucirumab (specifically for patients with AFP ≥400 ng/mL), regorafenib, and novel mechanisms in IO-pretreated patients. Locoregional + systemic trials are a major active space, testing IO before, during, or after transarterial chemoembolization (TACE) or radioembolization (Y-90 TARE) for patients with intermediate-stage disease. Adjuvant trials enroll patients post-resection or post-locoregional treatment, testing IO to prevent recurrence. CTNNB1-mutated (Wnt-class) trials test combinations to extend IO benefit in this resistant subset. HBV-positive HCC trials are a distinct space, including trials of HBV-targeted antiviral combinations and HBV vaccines for both prevention and treatment.

HCC trial eligibility centers on liver function, underlying disease etiology, and prior systemic therapy. Child-Pugh score is foundational for most HCC trials, with most trials requiring Child-Pugh A and some accepting Child-Pugh B7 (mild dysfunction). BCLC (Barcelona Clinic Liver Cancer) stage gates trials by disease extent and treatment intent (BCLC A early-stage curative-intent, BCLC B intermediate, BCLC C advanced systemic, BCLC D end-stage). Prior IO exposure for IO-pretreated trials. Prior TKI exposure for second-line and later trials. Prior locoregional therapy (TACE, TARE, ablation) and time since last locoregional procedure. Hepatitis B and C status with active or controlled disease distinctions; many trials require HBV under treatment if active. AFP level for ramucirumab-related trials. Variceal bleeding history and current variceal status. Performance status, with most trials accepting ECOG 0-1.

Biomarkers tested in Liver Cancer (HCC) trials

These are the molecular markers most commonly required or evaluated in Liver Cancer (HCC) eligibility criteria. OncoMatch extracts them from each trial's protocol and matches them against your test results.