NCT06698250

Zanzalintinib (XL-092) Plus Durvalumab and Tremelimumab in Unresectable Hepatocellular Carcinoma (ZENOBIA)

Phase II Trial of Zanzalintinib (XL-092) in Combination With Durvalumab Plus Tremelimumab in Unresectable Hepatocellular Carcinoma (ZENOBIA)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Anwaar Saeed · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will investigate if modulating the tumor microenvironment with biologic agents like XL-092 will have synergistic effect when combined with checkpoint based immunotherapeutic treatment of patients with hepatocellular carcinoma (HCC).

Detailed description

Zanzalintinib (XL-092) is a next generation tyrosine kinase inhibitor (TKI) with the target inhibition profile identical to cabozantinib but with a superior pharmacokinetic profile. As cabozantinib targets multiple tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR), MET proto-oncogene, receptor tyrosine kinase (MET), and AXL receptor tyrosine kinase (AXL), and has been reported to show immunomodulatory properties that may counteract tumor-induced immunosuppression, XL-092 is expected to have similar immune modulatory activity, providing a rationale for combining it with PD-1 or PD-L1 inhibitors. This study asserts the belief that modulating the tumor microenvironment with biologic agents like XL-092 will have synergistic effect when combined with checkpoint based immunotherapeutics like durvalumab and tremelimumab in patients with hepatocellular carcinoma (HCC). There will be a Safety lead-in to define the Recommended Phase 2 Dose (RP2D) that will enroll 6-12 patients.

Conditions

• Hepatocellular Carcinoma

Interventions

Type	Name	Description
DRUG	Zanzalintinib	Next generation tyrosine kinase inhibitor (TKI) with the target inhibition profile identical to cabozantinib but with a superior pharmacokinetic profile.
DRUG	Durvalumab	Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that blocks the interaction of programmed cell death ligand 1 (PD-L1) with the PD-1 (CD279)
DRUG	Tremelimumab	Tremelimumab is a fully human monoclonal antibody used for the treatment of hepatocellular carcinoma designed to attach to and block CTLA-4, a protein that controls the activity of T cells

Timeline

• Start date: 2024-12-18
• Primary completion: 2026-12-31
• Completion: 2027-04-30
• First posted: 2024-11-20
• Last updated: 2025-11-06

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study