Hepatocellular Carcinoma (HCC)Phase 2NCT07639138
Lenalidomide Plus Targeted Therapy and Immunotherapy for Refractory HCC
A Phase 2 study testing Lenalidomide, Targeted Therapy and Immune Checkpoint Inhibitors in people with Hepatocellular Carcinoma (HCC), run by Shunda Du at 1 site in China.
Trial summary
This is a prospective, single-arm, investigator-initiated clinical study designed to evaluate the safety and efficacy of lenalidomide in combination with targeted therapy and immunotherapy in patients with advanced hepatocellular carcinoma (HCC) who have experienced disease progression after multiple lines of systemic… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma (HCC)
- What is being tested?
- Lenalidomide, Targeted Therapy and Immune Checkpoint Inhibitors
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteChina
- Study dates
- 12 Aug 2026to 30 Jun 2030
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- -1. Age ≥18 years and ≤75 years; 2. Clinically or pathologically diagnosed hepatocellular carcinoma (HCC); 3. Unresectable, locally advanced, or metastatic HCC; 4. Prior receipt of at least two lines of systemic antitumor therapy, with previous exposure to both targeted therapy and immune checkpoint inhibitors (ICIs). No restrictions are imposed on the specific targeted agents or ICIs used in combination with lenalidomide; 5. Demonstrated clinical benefit from the most recent line of dual-agent therapy, defined as complete response (CR), partial response (PR), or stable disease (SD) lasting for at least 4 weeks, followed by radiographic progression or clinical treatment failure; 6. At least one measurable lesion according to RECIST version 1.1; 7. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1; 8. Adequate organ function, defined as: absolute neutrophil count (ANC) ≥1.0 × 10^9/L, platelet count ≥60 × 10^9/L, hemoglobin ≥80 g/L, creatinine clearance (CrCl) ≥30 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 × upper limit of normal (ULN), and total bilirubin ≤3 mg/dL; 9. Virological status, including hepatitis B virus (HBV) and hepatitis C virus (HCV), must be assessed. Patients who are HBsAg-positive or have a history of HBV infection must undergo hepatology evaluation and receive antiviral prophylaxis when indicated.
Who cannot join
- 1. Primary resistance to the most recent targeted therapy plus ICI regimen, defined as unequivocal disease progression within 6 weeks or 2 treatment cycles without any evidence of prior clinical benefit; 2. Prior exposure to lenalidomide or a history of severe hypersensitivity to lenalidomide or thalidomide; 3. Explosive disease progression, or situations in which continuation of the existing treatment backbone is deemed clinically unreasonable by the investigator; 4. Uncontrolled ascites, hepatic encephalopathy, or active gastrointestinal bleeding; active severe infections, including uncontrolled HBV replication, tuberculosis, severe pulmonary infection, or other serious infections; 5. Persistent treatment-related toxicities of grade ≥2 that have not recovered to baseline or acceptable levels at study entry; 6. Creatinine clearance (CrCl) <30 mL/min; 7. Pregnancy, breastfeeding, or inability/unwillingness to comply with contraceptive requirements.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Peking Union Medical College Hospital
Beijing, No. 1 Shuaifuyuan, Dongcheng District, Beijing, China, 100730
Longfang Miao, 010-69155709, pumchjyc@126.com
About this study
Official title: Safety and Efficacy of Lenalidomide Combined With Targeted Therapy and Immunotherapy in Patients With Advanced Hepatocellular Carcinoma Resistant to Multiple Prior Lines of Treatment: A Single-Center, Single-Arm, Prospective Exploratory Study
This is a prospective, single-arm, investigator-initiated clinical study designed to evaluate the safety and efficacy of lenalidomide in combination with targeted therapy and immunotherapy in patients with advanced hepatocellular carcinoma (HCC) who have experienced disease progression after multiple lines of systemic treatment.
Eligible patients must have received at least two prior lines of systemic therapy, including both targeted therapy and immune checkpoint inhibitor (ICI)-based treatment, and must have previously achieved clinical benefit from their most recent treatment regimen before developing disease progression.
Read more
Participants will continue their current targeted therapy and immunotherapy regimen and receive lenalidomide as add-on treatment. The study will assess antitumor activity, survival outcomes, and treatment-related adverse events.
The primary objectives are to evaluate 6-month progression-free survival (PFS) and the incidence of grade ≥3 treatment-related adverse events (TRAEs). Secondary objectives include objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and overall survival (OS).
Read the detailed description
Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide. Although targeted therapy and immune checkpoint inhibitors have significantly improved clinical outcomes, most patients eventually develop disease progression after multiple lines of treatment. Currently, there is no established standard therapy for patients with advanced HCC who have exhausted available targeted and immunotherapeutic options.
Lenalidomide is an immunomodulatory agent with antiangiogenic, immunoregulatory, and antitumor properties. Previous phase II studies have demonstrated modest clinical activity of lenalidomide in patients with advanced HCC who progressed after sorafenib treatment. However, the efficacy of lenalidomide as an add-on strategy in patients with advanced HCC who have previously benefited from targeted therapy and immunotherapy remains unknown.
This prospective, single-arm study aims to evaluate the safety and efficacy of lenalidomide combined with ongoing targeted therapy and immune checkpoint inhibitor treatment in patients with advanced, unresectable, locally advanced, or metastatic HCC who have experienced disease progression after at least two prior lines of systemic therapy.
Eligible patients must have previously achieved clinical benefit, defined as complete response (CR), partial response (PR), or stable disease (SD) lasting at least 4 weeks on their most recent targeted therapy plus immunotherapy regimen before progression. Patients with primary resistance to the most recent regimen will be excluded.
Participants will continue their most recent targeted therapy and immunotherapy regimen and receive lenalidomide until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision.
The co-primary endpoints are:
- Progression-free survival (PFS) rate at 6 months after treatment initiation; Incidence of grade ≥3 treatment-related adverse events (TRAEs), assessed according to CTCAE version 5.0.
- Secondary endpoints include objective response rate (ORR), disease control rate (DCR), duration of response (DoR), overall survival (OS), and additional safety outcomes.
The study is conducted at Peking Union Medical College Hospital and is expected to provide preliminary evidence regarding the potential role of lenalidomide in overcoming acquired resistance to targeted therapy and immunotherapy in advanced HCC.
- Conditions
- Hepatocellular Carcinoma (HCC)
- Being tested
- Lenalidomide, Targeted Therapy, Immune Checkpoint Inhibitors
- Keywords
- Advanced Hepatocellular Carcinoma, Multiline-Refractory HCC, Lenalidomide, Targeted Therapy, Immunotherapy
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenalidomideDrug
Lenalidomide administered orally in combination with ongoing targeted therapy and immunotherapy until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision.
Targeted TherapyDrug
Continuation of the most recent targeted therapy regimen that previously provided clinical benefit before disease progression.
Immune Checkpoint InhibitorsDrug
Continuation of the most recent immune checkpoint inhibitor regimen that previously provided clinical benefit before disease progression.
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide Combination Therapy | Experimental | Patients with advanced hepatocellular carcinoma who have progressed after multiple lines of systemic therapy will continue their current targeted therapy and immune checkpoint inhibitor regimen and receive lenalidomide as add-on treatment. Receives: Drug: Lenalidomide; Drug: Targeted Therapy; Drug: Immune Checkpoint Inhibitors |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Grade ≥3 Treatment-Related Adverse Events
Incidence of treatment-related adverse events of grade 3 or higher, assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measured: From treatment initiation until 30 days after treatment discontinuation
6-Month Progression-Free Survival Rate
Proportion of patients who remain alive without radiographic disease progression 6 months after treatment initiation, as assessed according to RECIST version 1.1.
Measured: 6 months after treatment initiation
Secondary outcomes (4)
Objective Response Rate
Measured: Up to 24 months
Disease Control Rate
Measured: Up to 24 months
Duration of Response
Measured: Up to 24 months
Overall Survival
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2026
- Study start12 Aug 2026
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma (HCC)Studies 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
- Model description
- This is a prospective, single-arm, open-label, phase II study evaluating the safety and efficacy of lenalidomide in combination with ongoing targeted therapy and immunotherapy in patients with advanced hepatocellular carcinoma who have progressed after multiple lines of systemic therapy.
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shunda Du
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Shunda Du, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07639138
- Sponsor's protocol ID
- I-26PJ1233
- Status last verified
- Jun 2026
- First submitted
- 5 Jun 2026
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Lenalidomide Combined With Targeted Therapy and Immunotherapy in Patients With Advanced Hepatocellular Carcinoma Resistant to Multiple Prior Lines of Treatment: A Single-Center, Single-Arm, Prospective Exploratory Study
- ClinicalTrials.gov ID
- NCT07639138
- Acronym / sponsor ID
- I-26PJ1233
- Conditions
- Hepatocellular Carcinoma (HCC)
- Keywords
- Advanced Hepatocellular Carcinoma, Multiline-Refractory HCC, Lenalidomide, Targeted Therapy, Immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Shunda DuUniversity, hospital or other
- Study start
- 12 Aug 2026 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Jun 2030 (estimated)
- First posted
- 10 Jun 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.
This is a prospective, single-arm, investigator-initiated clinical study designed to evaluate the safety and efficacy of lenalidomide in combination with targeted therapy and immunotherapy in patients with advanced hepatocellular carcinoma (HCC) who have experienced disease progression after multiple lines of systemic treatment.
Eligible patients must have received at least two prior lines of systemic therapy, including both targeted therapy and immune checkpoint inhibitor (ICI)-based treatment, and must have previously achieved clinical benefit from their most recent treatment regimen before developing disease progression.
Participants will continue their current targeted therapy and immunotherapy regimen and receive lenalidomide as add-on treatment. The study will assess antitumor activity, survival outcomes, and treatment-related adverse events.
The primary objectives are to evaluate 6-month progression-free survival (PFS) and the incidence of grade ≥3 treatment-related adverse events (TRAEs). Secondary objectives include objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and overall survival (OS).
Detailed description
Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide. Although targeted therapy and immune checkpoint inhibitors have significantly improved clinical outcomes, most patients eventually develop disease progression after multiple lines of treatment. Currently, there is no established standard therapy for patients with advanced HCC who have exhausted available targeted and immunotherapeutic options.
Lenalidomide is an immunomodulatory agent with antiangiogenic, immunoregulatory, and antitumor properties. Previous phase II studies have demonstrated modest clinical activity of lenalidomide in patients with advanced HCC who progressed after sorafenib treatment. However, the efficacy of lenalidomide as an add-on strategy in patients with advanced HCC who have previously benefited from targeted therapy and immunotherapy remains unknown.
This prospective, single-arm study aims to evaluate the safety and efficacy of lenalidomide combined with ongoing targeted therapy and immune checkpoint inhibitor treatment in patients with advanced, unresectable, locally advanced, or metastatic HCC who have experienced disease progression after at least two prior lines of systemic therapy.
Eligible patients must have previously achieved clinical benefit, defined as complete response (CR), partial response (PR), or stable disease (SD) lasting at least 4 weeks on their most recent targeted therapy plus immunotherapy regimen before progression. Patients with primary resistance to the most recent regimen will be excluded.
Participants will continue their most recent targeted therapy and immunotherapy regimen and receive lenalidomide until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision.
The co-primary endpoints are:
- Progression-free survival (PFS) rate at 6 months after treatment initiation; Incidence of grade ≥3 treatment-related adverse events (TRAEs), assessed according to CTCAE version 5.0.
- Secondary endpoints include objective response rate (ORR), disease control rate (DCR), duration of response (DoR), overall survival (OS), and additional safety outcomes.
The study is conducted at Peking Union Medical College Hospital and is expected to provide preliminary evidence regarding the potential role of lenalidomide in overcoming acquired resistance to targeted therapy and immunotherapy in advanced HCC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a prospective, single-arm, open-label, phase II study evaluating the safety and efficacy of lenalidomide in combination with ongoing targeted therapy and immunotherapy in patients with advanced hepatocellular carcinoma who have progressed after multiple lines of systemic therapy.
| Arm | Type | Receives |
|---|---|---|
| Lenalidomide Combination Therapy | Experimental | Drug: Lenalidomide, Drug: Targeted Therapy, Drug: Immune Checkpoint InhibitorsPatients with advanced hepatocellular carcinoma who have progressed after multiple lines of systemic therapy will continue their current targeted therapy and immune checkpoint inhibitor regimen and receive lenalidomide as add-on treatment. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- -1. Age ≥18 years and ≤75 years; 2. Clinically or pathologically diagnosed hepatocellular carcinoma (HCC); 3. Unresectable, locally advanced, or metastatic HCC; 4. Prior receipt of at least two lines of systemic antitumor therapy, with previous exposure to both targeted therapy and immune checkpoint inhibitors (ICIs). No restrictions are imposed on the specific targeted agents or ICIs used in combination with lenalidomide; 5. Demonstrated clinical benefit from the most recent line of dual-agent therapy, defined as complete response (CR), partial response (PR), or stable disease (SD) lasting for at least 4 weeks, followed by radiographic progression or clinical treatment failure; 6. At least one measurable lesion according to RECIST version 1.1; 7. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1; 8. Adequate organ function, defined as: absolute neutrophil count (ANC) ≥1.0 × 10^9/L, platelet count ≥60 × 10^9/L, hemoglobin ≥80 g/L, creatinine clearance (CrCl) ≥30 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 × upper limit of normal (ULN), and total bilirubin ≤3 mg/dL; 9. Virological status, including hepatitis B virus (HBV) and hepatitis C virus (HCV), must be assessed. Patients who are HBsAg-positive or have a history of HBV infection must undergo hepatology evaluation and receive antiviral prophylaxis when indicated.
Key exclusion criteria (1 listed)
- 1. Primary resistance to the most recent targeted therapy plus ICI regimen, defined as unequivocal disease progression within 6 weeks or 2 treatment cycles without any evidence of prior clinical benefit; 2. Prior exposure to lenalidomide or a history of severe hypersensitivity to lenalidomide or thalidomide; 3. Explosive disease progression, or situations in which continuation of the existing treatment backbone is deemed clinically unreasonable by the investigator; 4. Uncontrolled ascites, hepatic encephalopathy, or active gastrointestinal bleeding; active severe infections, including uncontrolled HBV replication, tuberculosis, severe pulmonary infection, or other serious infections; 5. Persistent treatment-related toxicities of grade ≥2 that have not recovered to baseline or acceptable levels at study entry; 6. Creatinine clearance (CrCl) <30 mL/min; 7. Pregnancy, breastfeeding, or inability/unwillingness to comply with contraceptive requirements.
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 |
|---|---|---|
| LenalidomideLenalidomide administered orally in combination with ongoing targeted therapy and immunotherapy until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. | Drug | Lenalidomide Combination Therapy |
| Targeted TherapyContinuation of the most recent targeted therapy regimen that previously provided clinical benefit before disease progression. | Drug | Lenalidomide Combination Therapy |
| Immune Checkpoint InhibitorsContinuation of the most recent immune checkpoint inhibitor regimen that previously provided clinical benefit before disease progression. | Drug | Lenalidomide Combination Therapy |
Primary outcome
Incidence of Grade ≥3 Treatment-Related Adverse Events
Time frame: From treatment initiation until 30 days after treatment discontinuation
Incidence of treatment-related adverse events of grade 3 or higher, assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
6-Month Progression-Free Survival Rate
Time frame: 6 months after treatment initiation
Proportion of patients who remain alive without radiographic disease progression 6 months after treatment initiation, as assessed according to RECIST version 1.1.
4 secondary outcomes
Objective Response Rate
Time frame: Up to 24 months
Disease Control Rate
Time frame: Up to 24 months
Duration of Response
Time frame: Up to 24 months
Overall Survival
Time frame: Up to 24 months
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 21 Sep 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Hepatocellular Carcinoma (HCC)
RecruitingPhase 2/3
A Study of VRT106, Combined With Camrelizumab, and Apatinib for Advanced HCC
HCC
Not yet recruitingObservational study
A Post Approval Study to Evaluate Safety and Effectiveness of Multicompartmental Dosimetry Planning.
Hepatocellular Carcinoma (HCC)
Active, not recruitingPhase 2
TheraSphere With Durvalumab and Tremelimumab for HCC
Hepatocellular Carcinoma
RecruitingPhase 1
A DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Glutamine Antagonist DRP-104, Nivolumab, and Ipilimumab in Patients With Advanced Stage Fibrolamellar Carcinoma (FLC)
Liver Cancer (Fibrolamellar Hepatocellular Cancer (FLC))
RecruitingPhase 2
DB-1311 in Combination With BNT327 or DB-1305 in Advanced/Metastatic Solid Tumors
Solid Tumors
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 Lenalidomide, Targeted Therapy and Immune Checkpoint Inhibitors in people with Hepatocellular Carcinoma (HCC), run by Shunda Du at 1 site in China.
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 1 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 21 Sep 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 China. 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 Jiayue Li (010-69156874, pumchkyc@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Grade ≥3 Treatment-Related Adverse Events (time frame: From treatment initiation until 30 days after treatment discontinuation). The study lists 2 primary outcomes in all. 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 21 Sep 2026; AzTrials last refreshed its copy on 31 Oct 2026.