Phase 1b (COSMIC-021) Trial of Cabozantinib Alone or in Combination With Atezolizumab in Patients With Solid Tumors Including Radioiodine (RAI)-Refractory Differentiated Thyroid Cancer (DTC)

    Background: VEGFR-targeted agents are standard of care for RAI-refractory DTC; however, treatment options are limited. Cabozantinib is an inhibitor of tyrosine kinases involved in tumor growth, including MET, VEGFR, and TAM kinases (Tyro3, AXL, MER). Cabozantinib promotes an immune-permissive tumor environment that may enhance response to immune checkpoint inhibitors, including anti–PD-L1 mAb atezolizumab. Cabozantinib has single-agent activity in patients with RAI-refractory DTC (Brose et al. ASCO 2018: Abstr 6088). We present the design of an ongoing phase 1b trial assessing cabozantinib+atezolizumab in patients with RAI-refractory DTC in the first-line setting. Methods: This global, multicenter, phase 1b, open-label trial is evaluating safety, tolerability, preliminary efficacy, and pharmacokinetics of cabozantinib or cabozantinib + atezolizumab in solid tumors (NCT03170960). The study comprises a dose-escalation stage and an expansion stage. The dose-escalation stage (3+3 design) is completed. Cabozantinib 40 mg qd + atezolizumab 1200 mg q3w is recommended for expansion. One of the 18 combination cohorts is assessing cabozantinib+atezolizumab in 30 patients with DTC (follicular, papillary, and poorly differentiated histologies) who are RAI-refractory or ineligible, naïve to systemic therapy, and receiving thyroxine suppression therapy. Patients will continue treatment as long as they experience clinical benefit or until unacceptable toxicity per investigator. The primary endpoint is the objective response rate per RECIST 1.1. Secondary objectives include assessment of immune-related adverse events. Results: This is an ongoing trial. Discussion & Conclusions: This study will provide safety and preliminary efficacy data on cabozantinib+atezolizumab in solid tumors, including DTC.


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