Carcinoma, HepatocellularPhase 2RECOMENDNCT07514455
Regorafenib After Treatment Failure of First Line Immune Checkpoint Inhibitor Treatment in Advanced Hepatocellular Carcinoma Patients
A Phase 2 study testing Regorafenib (BAY 73-4506) in people with Carcinoma, Hepatocellular and Hepatic Insufficien, run by Ju Hyun Shim at 1 site in South Korea.
Trial summary
Immune checkpoint inhibitor (ICI)-based regimens (atezolizumab+bevacizumab, durvalumab+tremelimumab, nivolumab+ipilimumab) are now a first-line standard for advanced hepatocellular carcinoma (HCC). Read more about this study
- Who is it for?
- Ages 19 to 80 years
- Conditions the study is for
- Carcinoma, Hepatocellular, Hepatic Insufficien, Disease Progression
- What is being tested?
- Regorafenib (BAY 73-4506)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteSouth Korea
- Study dates
- 15 Mar 2026to 30 Jun 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Voluntarily signed written informed consent form.
- Age ≥19 years at the time of signing the informed consent form.
- Histologically or clinically diagnosed hepatocellular carcinoma (HCC) according to the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) guidelines.
- Disease progression or treatment discontinuation due to toxicity during first-line immune checkpoint inhibitor-based combination therapy (atezolizumab plus bevacizumab, durvalumab plus tremelimumab, or nivolumab plus ipilimumab).
- At least one measurable target lesion according to RECIST v1.1.
- Child-Pugh score B (7-8).Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
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- Adequate hematologic and end-organ function defined by the following laboratory results obtained within 14 days prior to the test (or enrollment):
- Hemoglobin ≥ 8.5 g/dL
- Absolute Neutrophil Count (ANC) ≥1,200/mm³
- Platelet count ≥60,000/µL
- Total bilirubin < 3.5 mg/dL
- Serum albumin ≥2.5 g/dL
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤7 times upper limit of normal (ULN)
- Prothrombin time (INR ≤1.8 times ULN)
- Serum creatinine ≤2.0 times ULN or calculated creatinine clearance ≥40 mL/min (using the Cockcroft-Gault equation)
- 10) Virologic status of hepatitis confirmed and documented by HBV and HCV screening tests.Patients with HBV or HCV infection must receive antiviral therapy according to institutional guidelines.
- 11) Women of childbearing potential must agree to remain abstinent or use effective contraception (with an annual failure rate of < 1%) from the time of signing informed consent until at least 6 months after the last dose of the study drug.Male participants must agree to remain abstinent or use effective contraception (with an annual failure rate of < 1%) and refrain from sperm donation from the time of signing informed consent until at least 6 months after the last dose of the study drug.
Who cannot join
- ALBI (Albumin-Bilirubin) grade 3.
- Fibrolamellar carcinoma or sarcomatoid carcinoma.
- Prior treatment with regorafenib.
- Within 2 weeks since the last administration of an immune checkpoint inhibitor.
- Receipt of any other systemic or locoregional therapy after the failure of first-line immune checkpoint inhibitor-based therapy.
- History of allogeneic stem cell transplantation or solid organ transplantation.
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- Active brain metastases or leptomeningeal metastases.
- History of malignancy other than hepatocellular carcinoma (HCC) within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year survival rate > 90%).
- Severe cardiovascular disease within 3 months prior to the start of study therapy (e.g., New York Heart Association [NYHA] Class II or higher heart disease, myocardial infarction, or cerebrovascular accident); unstable arrhythmia or unstable angina; history of gastrointestinal perforation, fistula, or intra-abdominal abscess within 6 months prior to the start of study therapy; active gastrointestinal disease with a high risk of bleeding or perforation (e.g., peptic ulcer, inflammatory bowel disease, diverticulitis, cholecystitis, acute pancreatitis); untreated high-risk varices or recent history of variceal bleeding (enrollment is permitted only if at least 28 days have passed since stabilization with standard treatment); prolonged QTc interval (> 450 ms for males, > 470 ms for females); systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg despite optimal medical therapy; or other significant medical conditions or abnormal findings that, in the opinion of the investigator, may increase the risk associated with study participation.
- Female participants who are pregnant or breastfeeding, or male or female participants of reproductive potential who are unwilling to use effective contraception from screening until 6 months after the last dose of the study drug.
- Participants deemed by the investigator to be unlikely to comply with study procedures, restrictions, and requirements.
- Patients who have received locoregional therapy (e.g., radiofrequency ablation [RFA], microwave ablation [MWA], transarterial chemoembolization [TACE], transarterial radioembolization [TARE], transarterial embolization [TAE], radiation therapy, etc.) after the discontinuation of immune checkpoint inhibitor-based combination therapy.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea1 site
Asan Medical Center
Seoul, 05505
Ju Hyun Shim, MD PhD, 82-2-03103190, s5854@amc.seoul.kr
Sung Won Chung, MD, 82-2-3010-1105, schungaa@gmail.com
About this study
Official title: Regorafenib After Failure of First-Line Immune Checkpoint Inhibitor-Based Combination Therapy in Child-Pugh B Patients With HCC: A Phase 2 RECOMEND Trial
Immune checkpoint inhibitor (ICI)-based regimens (atezolizumab+bevacizumab, durvalumab+tremelimumab, nivolumab+ipilimumab) are now a first-line standard for advanced hepatocellular carcinoma (HCC). For Child-Pugh (CP) A patients, regorafenib, cabozantinib, and ramucirumab are approved second-line agents, but there is no approved second-line systemic therapy for CP-B. In CP-B historical controls treated with best supportive care, median progression free survival (PFS) was ~1.4 months in a REACH trial subgroup analysis and ~1.9 months in a CELESTIAL trial subgroup analysis. Regorafenib demonstrated benefit as a post-sorafenib second-line therapy in CP-A patients in the RESORCE trial, but prospective evidence in CP-B is lacking. A multicenter retrospective study of CP-B patients receiving second-line regorafenib after sorafenib reported a median PFS of 1.8 months, and prospective data after ICI-based first-line therapy are not available.
This study will evaluate the efficacy and safety of regorafenib as second-line therapy in CP-B patients with disease progression after first-line ICI-based treatment. The primary objective is to demonstrate superiority over historical controls, with PFS as the primary endpoint.
After written informed consent, all participants will receive regorafenib. Regorafenib will be administered at 120 mg orally once daily at the same time each day, after a meal with water, for 3 consecutive weeks followed by 1 week off (4-week cycle). Treatment must start within 3 days after screening and will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination, whichever occurs first. After treatment discontinuation, patients will be followed every 12 week (+/-7 days) for survival status and subsequent anticancer therapies, and survival follow-up will continue for at least 12 months after enrollment of the last participant.
- Being tested
- Regorafenib (BAY 73-4506)
- Medical subject headings
- Carcinoma, Hepatocellular, Disease Progression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Regorafenib (BAY 73-4506)Drug
Oral regorafenib 120 mg once daily, taken at the same time each day after a meal with water. The study drug is administered on a 28-day cycle, consisting of 3 consecutive weeks of daily dosing followed by 1 week off. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib | Experimental | Not described Receives: Drug: Regorafenib (BAY 73-4506) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
Measured: From treatment initiation until the date of first documented progression or death from any cause, whichever comes first, assessed up to 36 months.
Secondary outcomes (5)
Overall survival
Measured: From treatment initiation until the date of death from any cause, assessed up to 36 months.
time to progression
Measured: From treatment initiation until the date of first documented progression, assessed up to 36 months.
objective response rate
Measured: From treatment initiation until first documented progression or start of subsequent systemic anticancer therapy, assessed up to 36 months.
disease control rate
Measured: From treatment initiation until first documented progression or start of subsequent systemic anticancer therapy, assessed up to 36 months.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Adverse events will be graded according to the NCI CTCAE version 5.0.
Measured: From first dose of study drug until 30 days after last dose, assessed up to 36months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2026
- Study start15 Mar 2026 (estimated)
- Primary completion31 May 2028 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ju Hyun Shim
- Sponsor type
- University, hospital or other
- Collaborators
- Boryung Pharmaceutical Co., Ltd, National Cancer Center, Korea, Seoul National University Hospital, Seoul National University Bundang Hospital, Samsung Medical Center, Hanyang University Guri Hospital
- Responsible party
- Sponsor-investigator, Ju Hyun Shim, Asan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07514455
- Sponsor's protocol ID
- 2026-0244
- Acronym
- RECOMEND
- Status last verified
- Mar 2026
- First submitted
- 24 Mar 2026
- Last updated
- 7 Apr 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regorafenib After Failure of First-Line Immune Checkpoint Inhibitor-Based Combination Therapy in Child-Pugh B Patients With HCC: A Phase 2 RECOMEND Trial
- ClinicalTrials.gov ID
- NCT07514455
- Acronym / sponsor ID
- RECOMEND / 2026-0244
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Ju Hyun ShimUniversity, hospital or other
- Collaborators
- Boryung Pharmaceutical Co., Ltd, National Cancer Center, Korea, Seoul National University Hospital, Seoul National University Bundang Hospital, Samsung Medical Center, Hanyang University Guri Hospital
- Study start
- 15 Mar 2026 (estimated)
- Primary completion
- 31 May 2028 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 7 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Immune checkpoint inhibitor (ICI)-based regimens (atezolizumab+bevacizumab, durvalumab+tremelimumab, nivolumab+ipilimumab) are now a first-line standard for advanced hepatocellular carcinoma (HCC). For Child-Pugh (CP) A patients, regorafenib, cabozantinib, and ramucirumab are approved second-line agents, but there is no approved second-line systemic therapy for CP-B. In CP-B historical controls treated with best supportive care, median progression free survival (PFS) was ~1.4 months in a REACH trial subgroup analysis and ~1.9 months in a CELESTIAL trial subgroup analysis. Regorafenib demonstrated benefit as a post-sorafenib second-line therapy in CP-A patients in the RESORCE trial, but prospective evidence in CP-B is lacking. A multicenter retrospective study of CP-B patients receiving second-line regorafenib after sorafenib reported a median PFS of 1.8 months, and prospective data after ICI-based first-line therapy are not available.
This study will evaluate the efficacy and safety of regorafenib as second-line therapy in CP-B patients with disease progression after first-line ICI-based treatment. The primary objective is to demonstrate superiority over historical controls, with PFS as the primary endpoint.
After written informed consent, all participants will receive regorafenib. Regorafenib will be administered at 120 mg orally once daily at the same time each day, after a meal with water, for 3 consecutive weeks followed by 1 week off (4-week cycle). Treatment must start within 3 days after screening and will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination, whichever occurs first. After treatment discontinuation, patients will be followed every 12 week (+/-7 days) for survival status and subsequent anticancer therapies, and survival follow-up will continue for at least 12 months after enrollment of the last participant.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Regorafenib | Experimental | Drug: Regorafenib (BAY 73-4506) |
Who may qualify
- Ages
- 19 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Voluntarily signed written informed consent form.
- Age ≥19 years at the time of signing the informed consent form.
- Histologically or clinically diagnosed hepatocellular carcinoma (HCC) according to the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) guidelines.
- Disease progression or treatment discontinuation due to toxicity during first-line immune checkpoint inhibitor-based combination therapy (atezolizumab plus bevacizumab, durvalumab plus tremelimumab, or nivolumab plus ipilimumab).
- At least one measurable target lesion according to RECIST v1.1.
Key exclusion criteria (12 listed)
- ALBI (Albumin-Bilirubin) grade 3.
- Fibrolamellar carcinoma or sarcomatoid carcinoma.
- Prior treatment with regorafenib.
- Within 2 weeks since the last administration of an immune checkpoint inhibitor.
- Receipt of any other systemic or locoregional therapy after the failure of first-line immune checkpoint inhibitor-based therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Regorafenib (BAY 73-4506)Oral regorafenib 120 mg once daily, taken at the same time each day after a meal with water. The study drug is administered on a 28-day cycle, consisting of 3 consecutive weeks of daily dosing followed by 1 week off. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. | Drug | Regorafenib |
Primary outcome
Progression Free Survival
Time frame: From treatment initiation until the date of first documented progression or death from any cause, whichever comes first, assessed up to 36 months.
5 secondary outcomes
Overall survival
Time frame: From treatment initiation until the date of death from any cause, assessed up to 36 months.
time to progression
Time frame: From treatment initiation until the date of first documented progression, assessed up to 36 months.
objective response rate
Time frame: From treatment initiation until first documented progression or start of subsequent systemic anticancer therapy, assessed up to 36 months.
disease control rate
Time frame: From treatment initiation until first documented progression or start of subsequent systemic anticancer therapy, assessed up to 36 months.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From first dose of study drug until 30 days after last dose, assessed up to 36months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Regorafenib (BAY 73-4506) in people with Carcinoma, Hepatocellular and Hepatic Insufficien, run by Ju Hyun Shim at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 7 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ju Hyun Shim, MD PhD (82230103190, s5854@amc.seoul.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (time frame: From treatment initiation until the date of first documented progression or death from any cause, whichever comes first, assessed up to 36 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2026.