CXD101 treatment for liver cancer resistant to immunotherapy
Epigenetic Therapeutics to Overcome Resistance Against Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: A Proof-of-concept Clinical Trial
This study is testing a new treatment combining CXD101 and geptanolimab to see if it can help people with liver cancer who haven't responded to other immunotherapy options.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 44 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Chinese University of Hong Kong Academic / other |
| Drugs / interventions | lenvatinib, pembrolizumab, geptanolimab, atezolizumab, bevacizumab |
| Locations | 2 sites (Hong Kong and 1 other locations) |
| Trial ID | NCT05873244 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the efficacy of CXD101, a class 1 HDAC inhibitor, combined with the anti-PD1 agent geptanolimab in patients with hepatocellular carcinoma (HCC) who have shown resistance to prior immune checkpoint inhibitor treatments. Participants will be randomized into two groups: one receiving the experimental combination therapy and the other receiving standard treatments like lenvatinib or sorafenib. The primary goal is to assess progression-free survival, with additional tumor biopsies taken to identify potential predictive biomarkers. This approach aims to validate previous findings on the role of HDACs in mediating resistance to immunotherapy in HCC patients.
Who should consider this trial
Good fit: Ideal candidates are patients diagnosed with HCC who have previously received immune checkpoint inhibitors and have experienced disease progression.
Not a fit: Patients who have not undergone prior treatment with immune checkpoint inhibitors or those with severe autoimmune diseases may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for HCC patients who have not responded to existing immunotherapies.
How similar studies have performed: Other studies have shown promise in using HDAC inhibitors in combination with immunotherapy, suggesting potential success for this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Diagnosis of HCC according to the AASLD guideline20 * Prior treatment with systemic treatment consisting of immune checkpoint inhibitors (anti-PD1, anti-PDL1 or anti-CTLA4) * The duration of previous ICI must be 6 weeks or longer to avoid chance of pseudo-progression * Eastern Cooperative Oncology Group (ECOG) Performance status of 0-1 * Adequate hematological function: * Absolute neutrophil count (ANC) ≥ 1.5 x109/L; Platelets ≥ 100 x 109/L and Hemoglobin ≥ 8g/dL * Adequate renal function: * Urine protein/creatinine ratio ≤ 1 mg/mg (≤ 113.1 mg/mmol) or 24-hour urine protein \< 1g * Serum creatinine ≤ 1.5 × upper limit of normal or calculated creatinine clearance ≥ 40 mL/min (according to the Cockcroft-Gault equation) * Adequate hepatic function parameters: * Total bilirubin ≤ 2 mg/dL (≤ 34.2 μmol/L) * Serum albumin ≥ 2.8 g/dL (≥ 28 g/L) * Alanine aminotransferase (ALT) \< 3.0 upper limit of normal (ULN) Exclusion Criteria: * Previous development of severe autoimmune complications from immune checkpoint inhibitors * History of moderate to sever autoimmune disease requiring steroid use * History of organ transplant * Prior use of lenvatinib or sorafenib * Disease involvement/thrombosis of major vessels (including main trunk of portal vein, inferior vena cava or pulmonary artery) * More than two lines of systemic therapy (i.e., study treatment must be second-line or third-line treatment) * Clinically significant bleeding events (eg.. esophageal varices) within 3 months * Moderate or severe ascites * Child-pugh B or C hepatic function * Systolic blood pressure of 200mmHg or higher * Pregnant or lactating females
Where this trial is running
Hong Kong and 1 other locations
- Department of Clinical Oncology, Prince of Wales Hospital — Hong Kong, Hong Kong (Recruiting)
- School of Biomedical Science, The Chinese University of Hong Kong — Hong Kong, Hong Kong (Active_not_recruiting)
Study contacts
- Study coordinator: Stephen Chan, MD, FRCP
- Email: chanlam_stephen@cuhk.edu.hk
- Phone: 3505 2166
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.