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AzTrials

HCCPhase 2NCT05873244

CXD101 in Immunotherapy-related Liver Cancer

A Phase 2 study testing Zabadinostat (CXD101) and Geptanolimab and Lenvatinib and Sorafenib in people with HCC, run by Stephen Chan Lam at 2 sites in Hong Kong.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HCC
What is being tested?
Zabadinostat (CXD101) and Geptanolimab and Lenvatinib and Sorafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
2 sitesHong Kong
Study dates
21 Aug 2023to 30 Dec 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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

2 sites in 1 country.

Hong Kong2 sites

  • Department of Clinical Oncology, Prince of Wales Hospital

    Hong Kong

  • School of Biomedical Science, The Chinese University of Hong Kong

    Hong Kong

Other trials in Hong Kong

About this study

Official title: Epigenetic Therapeutics to Overcome Resistance Against Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: A Proof-of-concept Clinical Trial

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.

Read the detailed description

To move from bench to clinic, it is crucial to validate the above in HCC patients demonstrating resistance to ICI-based treatment. In this grant, the investigators propose a randomized phase II clinical trial in patients with HCC who developed progressive disease to prior regimen containing anti-PD(L)-1. The investigators have already secured support of study medications from two pharmaceuticals to provide class 1 HDAC inhibitor and anti-PD1, respectively. Patients were randomized 1:1 to two study arms: the experiment arm consists of CXD101 20mg twice daily Day 1-5 every 3 weeks and an anti-PD1, geptanolimab at 3mg/kg Day 1 every 2 weeks. The dose of CXD101 has already been confirmed to be safe to combine with anti-PD1 in phase I/II studies in cancer patients. The control arm consists of investigators' choice of lenvatinib or sorafenib which are both considered standard treatment after failure with first-line atezolizumab-bevacizumab or other anti-PD(L)-1-based treatment. The primary endpoint is progress-free survival. Along the clinical trial, tumor biopsy will also be conducted at baseline and 6-week post-treatment to explore potential predictive biomarkers. Results of the study not only act as proof-of-concept but also potentially develop a novel treatment combination to tackle resistance to anti-PD(L)-1 treatment in HCC.

Conditions
HCC
Being tested
Zabadinostat (CXD101) and Geptanolimab, Lenvatinib and Sorafenib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Zabadinostat (CXD101) and GeptanolimabDrug

    • Zabadinostat (CXD101) at 20mg twice daily per orally Day 1-5 every 3 weeks
    • Geptanolimab at 3mg/kg given intravenously every 2 weeks

  • Lenvatinib and SorafenibDrug

    Clinicians' choice of TKI at corresponding recommended dosage:

    • Lenvatinib at 8mg daily for patients with body weight <60kg or 12mg daily with body weight ≥ 60kg
    • Sorafenib at 400mg twice daily
Study groups in NCT05873244
Study groupRoleWhat they receive
Experiment armExperimental* Zabadinostat (CXD101) at 20mg twice daily per orally Day 1-5 every 3 weeks * Geptanolimab at 3mg/kg given intravenously every 2 weeks
Receives: Drug: Zabadinostat (CXD101) and Geptanolimab
Control armOtherClinicians' choice of TKI at corresponding recommended dosage: * Lenvatinib at 8mg daily for patients with body weight <60kg or 12mg daily with body weight ≥ 60kg * Sorafenib at 400mg twice daily
Receives: Drug: Lenvatinib and Sorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The progression-free survival in HCC patients treated with CXD101 plus Geptanolimab and control arm

    Measured: 2 years

Secondary outcomes (4)

  1. The overall survival in HCC patients treated with CXD101 plus Geptanolimab and control arm

    Measured: 2 years

  2. The radiological response rate in HCC patients treated with CXD101 plus Geptanolimab and control arm

    Measured: 2 years

  3. The time-to-progression in HCC patients treated with CXD101 plus Geptanolimab and control arm

    Measured: 2 years

  4. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 May 2023
  2. Study start21 Aug 2023
  3. Primary completion30 Dec 2027 (estimated)
  4. Study completion30 Dec 2028 (estimated)

Resources

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05873244
Sponsor's protocol ID
HCC074
Status last verified
Jun 2026
First submitted
3 May 2023
Last updated
18 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Tu Y, Wu H, Zhong C, Liu Y, Xiong Z, Chen S, Wang J, Wong PP, Yang W, Liang Z, Lu J, Chen S, Zhang L, Feng Y, Si-Tou WW, Yin B, Lin Y, Liang J, Liang L, Vong JSL, Ren W, Kwong TT, Leung H, To KF, Ma S, Tong M, Sun H, Xia Q, Zhou J, Kerr D, La Thangue N, Sung JJY, Chan SL, Cheng AS. Pharmacological activation of STAT1-GSDME pyroptotic circuitry reinforces epigenetic immunotherapy for hepatocellular carcinoma. Gut. 2025 Mar 6;74(4):613-627. doi: 10.1136/gutjnl-2024-332281.

    PubMed 39486886

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zabadinostat (CXD101) and Geptanolimab and Lenvatinib and Sorafenib in people with HCC, run by Stephen Chan Lam at 2 sites in Hong Kong.

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 13 inclusion and 11 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: under way, not looking for participants, as of the sponsor's last update on 18 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Hong Kong. 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The progression-free survival in HCC patients treated with CXD101 plus Geptanolimab and control arm (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05873244, which also lists 1 linked publication.

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 18 Jun 2026.

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