STELLAR-305: phase II/III study of zanzalintinib plus pembrolizumab versus pembrolizumab alone in patients with HNSCC

Future Oncol. 2025 May;21(11):1349-1356. doi: 10.1080/14796694.2025.2485015. Epub 2025 Apr 18.

Abstract

Tweetable abstract: STELLAR-305: design of an ongoing phase III #clinicaltrial, assessing the multi-targeted tyrosine kinase inhibitor, zanzalintinib, in combination with pembrolizumab in previously untreated recurrent/metastatic #HNSCC.

Clinical trial registration: NCT06082167 (ClinicalTrials.gov).

Keywords: HNSCC; Head and neck squamous cell carcinoma; XL092; immune checkpoint inhibitor; pembrolizumab; phase II/III; tyrosine kinase inhibitor; zanzalintinib.

Plain language summary

Flat cells that line the surfaces of the mouth, throat, and voice box are called squamous cells. Head and neck cancers usually begin in these cells and are referred to as squamous cell carcinomas of the head and neck, or HNSCC. People with advanced HNSCC that has come back after prior treatment or has spread from where it started to other parts of the body are usually treated with chemotherapy, which kills cancer cells, and/or a treatment known as an immune checkpoint inhibitor (ICI), which works by helping the body’s own immune system attack cancer cells. However, these treatments might not control the cancer and/or can cause side effects that negatively affect a person’s life. New treatments are therefore needed. Zanzalintinib is a drug taken by mouth that is being investigated as a treatment to reduce cancer cells or stop them growing and spreading, and it may help improve the body’s response to an ICI. STELLAR-305 is a study that will test how well zanzalintinib given with an ICI called pembrolizumab controls HNSCC compared with pembrolizumab on its own. The study will include people who have not been previously treated for advanced HNSCC, or who were treated before their cancer spread. Researchers will look at how long participants stay alive without their cancer getting worse and the length of time they stay alive after starting treatment. Additionally, the side effects of treatment will be monitored. Approximately 600 participants will be included in the study from several countries across the world.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Female
  • Head and Neck Neoplasms* / drug therapy
  • Head and Neck Neoplasms* / mortality
  • Head and Neck Neoplasms* / pathology
  • Humans
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Protein Kinase Inhibitors / administration & dosage
  • Randomized Controlled Trials as Topic
  • Squamous Cell Carcinoma of Head and Neck* / drug therapy
  • Squamous Cell Carcinoma of Head and Neck* / mortality
  • Squamous Cell Carcinoma of Head and Neck* / pathology
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • pembrolizumab
  • Protein Kinase Inhibitors

Associated data

  • ClinicalTrials.gov/NCT06082167