NCT05873244Active, not recruitingPhase 2
CXD101 in Immunotherapy-related Liver Cancer
Epigenetic Therapeutics to Overcome Resistance Against Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: A Proof-of-concept Clinical Trial
Source: ClinicalTrials.gov · Last updated 18 Jun 2026
Brief summary (registry, in English)
For hepatocellular carcinoma (HCC), durable responses and improved survivals have been reported in clinical trials on immune checkpoint inhibitor (ICI)-based treatment. However, resistance to ICI is increasingly encountered in clinical practice in HCC patients. Various approaches are currently evaluated in clinical setting to tackle acquired resistance during treatment of ICIs in HCC. Our group has a track record of studying the role of histone deacetylases (HDACs) in mediating resistance to ICI in HCC. First, based on single-cell sequencing data of serial biopsy of tumor in our phase II clinical trial on pembrolizumab in HCC (NCT03419481), the investigators reveal an upregulation of class 1 HDAC in patients with acquired resistance to pembrolizumab, which was associated with reduced lymphoid/myeloid cellular ratio in the tumor. Further, the investigators showed that HDAC8, a class 1 HDAC, could diminish the efficacy of anti-programmed cell death (ligand)-1 (PD\[L\]-1) by the mechanism of T-cell exclusion from the tumor environment (SciTranl Med. 2021;13:online). Finally, the investigators combine CXD101, a potent selective class I HDAC inhibitor, with anti-PD(L)-1 in orthotopic immunocompetent HCC mouse model with resistance to anti-PD(L)-1 treatment and find that the combination regimen could reverse the resistance phenotype and significantly improve survivals of mice than either CXD101 or anti-PD(L)-1 alone.
- Status (registry)
- Active, not recruiting
- Phase (registry)
- Phase 2
- Study type
- Interventional
- Enrollment
- 26 (actual)
- First submitted
- 3 May 2023
- Start date
- 21 Aug 2023
- Primary completion date
- 30 Dec 2027
- Lead sponsor
- Stephen Chan Lam
- Diseases
- Liver and biliary tract cancer
- NCT number
- NCT05873244
What you commit to
- Study type: Interventional · Phase 2
- Participants enrolled: 26
- From 21 Aug 2023 to the primary completion date, 30 Dec 2027
- 2 sites in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- Previous development of severe autoimmune complications from immune checkpoint inhibitors
- Prior use of lenvatinib or sorafenib
- More than two lines of systemic therapy (i.e., study treatment must be second-line or third-line treatment)
Other illness
- History of moderate to sever autoimmune disease requiring steroid use
- History of organ transplant
- Disease involvement/thrombosis of major vessels (including main trunk of portal vein, inferior vena cava or pulmonary artery)
- Clinically significant bleeding events (eg.. esophageal varices) within 3 months
Other
- Moderate or severe ascites
- Child-pugh B or C hepatic function
- Systolic blood pressure of 200mmHg or higher
- Pregnant or lactating females
Who the study is looking for
- 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)
Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers
Sites (2)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| Department of Clinical Oncology, Prince of Wales Hospital Coordinator of this site? Confirm its status | Hong Kong | Hong Kong SAR China | Unknown status |
| School of Biomedical Science, The Chinese University of Hong Kong Coordinator of this site? Confirm its status | Hong Kong | Hong Kong SAR China | Unknown status |
This page is information, not medical advice. Discuss any trial with your doctor.