Clinical trial · Interventional
Regorafenib-pembrolizumab vs. TACE/TARE in Intermediate Stage HCC Beyond Up-to-7
A Phase III, Multicenter, Randomized, Open-label Trial to Evaluate the Safety and Efficacy of Systemic Therapy With Regorafenib and Pembrolizumab Versus Locoregional Therapy With Transarterial Chemoembolization or Transarterial Radioembolization, for the First-line Treatment of Intermediate-stage Hepatocellular Carcinoma With Beyond Up-to-7 Criteria
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): The trial ended earlier than planned due to slow enrolment, which has made it unfeasible to achieve the target sample size within a reasonable timeframe. Consequently, a business decision has been made to discontinue funding for the trial.
Summary
Brief summary (as posted)
REPLACE is a phase III, multicenter, randomized, open-label trial to evaluate the efficacy and safety of regorafenib and pembrolizumab (Rego-Pembro) versus transarterial chemoembolization (TACE) or transarterial radioembolization (TARE) for the first-line treatment of hepatocellular carcinoma (HCC or liver cancer). Approximately 496 patients in around 80 clinical sites worldwide will be randomized to receive either: * Investigational arm: Regorafenib in combination with pembrolizumab * Control arm: Transarterial chemoembolization (TACE) or transarterial radioembolization (TARE) In both arms, patients will receive trial treatment until progressive disease, unacceptable toxicity, deterioration of patient's condition that warrants permanent trial treatment discontinuation or other treatment discontinuation criteria is met. After trial treatment discontinuation, subsequent treatment will be administered according to the Investigator's clinical judgment.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Carcinoma, Hepatocellular | Hepatocellular Carcinoma | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Loco-regional therapy | Procedure | — | UNRESOLVED |
| Regorafenib in combination with pembrolizumab | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Regorafenib + Pembrolizumab
- description
- Investigational arm: regorafenib at a dose of 90 mg orally once per day (on days 1 to 21 of a 28-day cycle), in combination with pembrolizumab 400 mg using a 30-minute intravenous infusion, on day 1 of a 6-week cycle.
- interventionNames
- Drug: Regorafenib in combination with pembrolizumab
- type
- ACTIVE_COMPARATOR
- label
- Loco-regional therapy
- description
- Control arm: Patients will be treated with TACE or TARE "on-demand" according to site's standard of practice.
- interventionNames
- Procedure: Loco-regional therapy
Primary outcomes (1)
- measure
- Progression-free Survival (PFS) Assessed by the Investigator as per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) for HCC
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Signed and dated Patient Informed Consent Form (PICF) * ≥ 18 years-old at the time of PICF signature * Confirmed diagnosis of HCC * Intermediate-stage HCC, defined as follows: * Multinodular HCC localized to the liver * No evidence of MVI or EHS * Not amenable to curative treatment * Child-Pugh Class A * ECOG PS 0 or 1 * ALBI grade 1 or 2 * Beyond up-to-seven criteria * Disease amenable to TACE or TARE and no contradiction to intra-arterial treatment * Measurable disease by CT or MRI as per RECIST 1.1 * No prior systemic therapy or loco-regional therapy for HCC * Adequate hematologic and organ function * Willing and able to comply with scheduled visits, treatment plans, laboratory tests and other trial procedures * Women of childbearing potential (CBP) must have confirmed negative serum pregnancy test * Use of highly-effective contraceptive methods in women of CBP and men * Patients with hepatitis C virus (HCV) or hepatitis B virus (HBV) infection are eligible if they meet criteria as defined within the protocol Exclusion Criteria: * No measurable tumor of a diffuse infiltrative HCC type. * Fibrolamellar HCC, sarcomatoid HCC or mixed hepatocellular/ cholangiocarcinoma subtypes. * Clinically meaningful ascites. * Prior treatment with regorafenib, a PD-1, PD-L1/PD-L2, or cytotoxic T lymphocyte associated protein 4 (CTLA-4) inhibitors, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. * Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior to randomization. * Active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. * Requirement of systemic treatment with either corticosteroids or other immunosuppressive medications ≤ 14 days prior to randomization. * Interstitial lung disease, non-infectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, or clinically significant acute lung diseases. * Cardiovascular conditions as defined within the protocol. * Patient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed ≤ 2 years before randomization. * Persistent proteinuria of NCI-CTCAE v5.0 Grade 3. * Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial.
References
Publications (0)
Data not yet available