Phase II Trial of Zanzalintinib (XL-092) in Combination With Durvalumab Plus Tremelimumab in Unresectable Hepatocellular Carcinoma (ZENOBIA)
Anwaar Saeed
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).
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 w…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Patients must have unresectable hepatocellular carcinoma. 2. Patients must be treatment naïve for systemic therapy in the unresectable setting. 3. ≥ 18 years and ECOG performance status 0-1 4. Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from adverse events (AEs), unless AE(s) are clinically nonsignificant and/or stable on supportive therapy (e.g., physiological replacement of mineralocorticosteroid). 5. Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment. 6. Urine pro…
Interventions
- DrugZanzalintinib
Next generation tyrosine kinase inhibitor (TKI) with the target inhibition profile identical to cabozantinib but with a superior pharmacokinetic profile.
- DrugDurvalumab
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)
- DrugTremelimumab
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
Locations (3)
- UPMC Hillman Cancer CenterPittsburgh, Pennsylvania
- Houston Methodist Neal Cancer CenterHouston, Texas
- Mays Cancer Center, UT Health San AntonioSan Antonio, Texas