NCT07470489

Zanzalintinib Plus Cemiplimab for the Treatment of BRAF Wild-Type Anaplastic Thyroid Cancer

A Multi-Center Single-Arm Phase 2 Trial Of Zanzalintinib In Combination With Cemiplimab In BRAF Wild-Type Anaplastic Thyroid Cancer: The ZEPHYR Trial

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of the trial is to improve this OS by 4 months (to 9.9 months) using the zanzalintinib + cemiplimab treatment combination. Given an accrual period of 24 months and a maximum follow-up time of 36 months, at the significance level of 0.1, to achieve the power of 0.8, the sample size needed is 24 patients and the number of events required is 17. These results are based on a one-sided test with exponential assumption for survival time.

Detailed description

Primary Objective: The study's primary objective is to determine the overall survival (OS) of zanzalintinib plus cemiplimab in treatment-naïve BRAF wild type ATC patients. Secondary Objectives: * Determine the 6-month OS rate with zanzalintinib plus cemiplimab in treatment-naïve BRAF wild type ATC patients * Determine the objective response rate (ORR) and progression-free survival (PFS) in patients treated with zanzalintinib plus cemiplimab, per RECIST v1.1 * Determine the metabolic response rate (MRR) to zanzalintinib plus cemiplimab, per PERCIST 1.0 in patients undergoing serial 18F-FDG PET/CT imaging * Establish safety for concurrent administration of zanzalintinib plus cemiplimab * Evaluate the Quality of Life (QoL) of patients with ATC treated with zanzalintinib plus cemiplimab Exploratory Objectives: * Assess response of locoregional disease to zanzalintinib plus cemiplimab in the subgroup of patients who underwent palliative neck RT prior to or within the first month of trial enrollment. This will be determined by the ORR of the neck disease per modified neck RECIST and PERCIST. * Determine whether features of the tumor genomic landscape and tumor immune microenvironment are associated with response and survival outcomes with zanzalintinib plus cemiplimab * Determine whether baseline PD-L1 expression and NLR correlate with response to zanzalintinib plus cemiplimab and survival outcomes. * Evaluate if ctDNA changes and presence of MRD correlate with response to zanzalintinib plus cemiplimab and survival outcomes. * Investigate the immunomodulatory effects of palliative-dose radiation in ATC * Determine whether systemic immune dynamics predict response to zanzalintinib plus cemiplimab

Conditions

• Anaplastic Thyroid Cancer

Interventions

Type	Name	Description
DRUG	Cemiplimab	Given by IV
DRUG	Zanzalintinib	Given by IV

Timeline

• Start date: 2026-09-30
• Primary completion: 2030-09-01
• Completion: 2032-09-01
• First posted: 2026-03-13
• Last updated: 2026-04-16

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study