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CXD101 in Immunotherapy-related Liver Cancer

NCT05873244 · Status: RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 44

Last updated 2025-03-21

No results posted yet for this study

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.

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.

Conditions

Interventions

DRUG

Zabadinostat (CXD101) and Geptanolimab

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

DRUG

Lenvatinib and Sorafenib

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

Sponsors & Collaborators

  • Stephen Chan Lam

    lead OTHER

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2023-08-21
Primary Completion
2026-12-30
Completion
2027-12-30

Countries

  • Hong Kong

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05873244 on ClinicalTrials.gov