Lenalidomide Plus Targeted Therapy and Immunotherapy for Refractory HCC

NCT07639138 | Recruiting Phase 2 DMC

• 1 other identifier: I-26PJ1233
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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 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).

Conditions

Hepatocellular Carcinoma (HCC)

Keywords

Advanced Hepatocellular Carcinoma; Multiline-Refractory HCC; Lenalidomide; Targeted Therapy; Immunotherapy

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  6 months after treatment initiation

Secondary Outcomes (4)

• Objective Response Rate

  Up to 24 months

• Disease Control Rate

  Up to 24 months

• Duration of Response

  Up to 24 months

• Overall Survival

  Up to 24 months

Study Arms (1)

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.

Drug: Lenalidomide; Drug: Targeted Therapy; Drug: Immune Checkpoint Inhibitors

Interventions

Targeted Therapy DRUG

Continuation of the most recent targeted therapy regimen that previously provided clinical benefit before disease progression.

Lenalidomide Combination Therapy

Lenalidomide DRUG

Lenalidomide administered orally in combination with ongoing targeted therapy and immunotherapy until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision.

Lenalidomide Combination Therapy

Immune Checkpoint Inhibitors DRUG

Continuation of the most recent immune checkpoint inhibitor regimen that previously provided clinical benefit before disease progression.

Lenalidomide Combination Therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \. 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.

Sponsors & Collaborators

• Shunda Du: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, No. 1 Shuaifuyuan, Dongcheng District, Beijing, China, 100730, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Lenalidomide; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Jiayue Li

CONTACT

010-69156874; pumchkyc@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: June 5, 2026
• First Posted: June 10, 2026
• Study Start: June 10, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2030
• Last Updated: June 10, 2026

Record last verified: 2026-06

Locations

CN (1)