Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May;21(11):1349-1356.
doi: 10.1080/14796694.2025.2485015. Epub 2025 Apr 18.

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

Nabil F Saba  1   2 , Kevin Harrington  3   4 , Lisa Licitra  5   6 , Jean-Pascal Machiels  7   8 , Cixin He  9 , Taylor Jew  9 , Vasily Andrianov  9 , Robert Haddad  10
Affiliations

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

Nabil F Saba et al. Future Oncol. 2025 May.

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.

PubMed Disclaimer

Conflict of interest statement

Nabil F. Saba reports research funding from Exelixis. Reports compensated and non compensated advisory roles from: Astra Zeneca, Eisai, EMD Serono, Merck, Vaccinex, CUE, BionTech, GSK, Seagen, FLamingo, Infinity, Inovio, Aveo, Uptodate, BMS, Surface Oncology, Urogen and funding from BMS.

Kevin Harrington reports research funding (paid to institution) from AstraZeneca, Boehringer Ingelheim, and Replimune; consulting/advisory roles (paid to institution) for ALX Oncology, Arch Oncology, AstraZeneca, Beigene, Boehringer Ingelheim, Codiak, Exelixis, F-star, GSK, Inzen, Johnson & Johnson, Merck-Serono, Merck & Co., Inc., Rahway, NJ, USA, Nanobiotix, Pfizer, Replimune, and QBiotics; and honoraria (paid to institution) from Boehringer Ingelheim, Merck-Serono, Merck & Co., Inc., Rahway, NJ, USA, and Replimune.

Lisa Licitra reports research funding (paid to institution) from Adlai Nortye, AstraZeneca, BMS, Debiopharm International SA, Eisai, Eli Lilly and Co., Exelixis, F. Hoffman-La Roche, Genmab, Gilead Sciences, Incyte, Isa Therapeutics, Kura Oncology, Merck Healthcare KGaA, Merck Serono, Merck & Co., Inc., Rahway, NJ, USA, Nektar Therapeutics, Novartis, Regeneron, Roche, Sanofi, Syneos, and Sun Pharmaceutic; consulting/advisory roles for ALX Oncology, Boehringer Ingelheim, EMD Serono Research & Development Institute, groupH Ltd, Merck Serono Spa Healthcare Professional, Merck Healthcare KGaA, GSK, F. Hoffman-La Roche, and SD IT; honoraria from Adlai Nortye, ALTIS Omnia Pharma Service Sàrl, BMS, Merck Serono Spa, MSD IT, Merck Healthcare KGaA; travel/accommodation expenses from TAE Life Science; and participation on a data safety monitoring board or advisory board for AbbVie, AstraZeneca, Eisai, EMD Serono, F. Hoffman-La Roche, Genmab, Janssen, Merck & Co., Inc., Rahway, NJ, USA, Merck Healthcare, Mirati Therapeutics, MSD IT, Neutron Therapeutics, Novartis, and Seagen.

Jean-Pascal Machiels reports consulting/advisory roles (paid to institution) for ALX Oncology, Astellas, Bayer, BMS, Boehringer Ingelheim, Cue Biopharma, CureVac, eTheRNA, F-Star, Genmab, GSK, Incyte, IPSEN, iTEOS, Merck Serono, Merus, Merck & Co., Inc., Rahway, NJ, USA, NEKTAR, Novartis, Pfizer, Roche, and Seagen; and travel expenses from Amgen, BMS, Gilead, MSD, Pfizer, and Sanofi.

Cixin He, Taylor Jew, and Vasily Andrianov are employees of and hold stock/share options in Exelixis.

Robert Haddad reports research funding from AstraZeneca, EMD Serono, Exelixis, Genentech, GSK, Incyte, IO Biotech, Kura, Merck, and Merus; consulting/advisory roles for AstraZeneca, Bayer, EMD Serono, Genmab, Merck, PDS, and RAPT; and participation on a data safety monitoring board or advisory board for Hookipa, ISA, and Nanobiotix.

References

    1. Gormley M, Creaney G, Schache A, et al. Reviewing the epidemiology of head and neck cancer: definitions, trends and risk factors. Br Dent J. 2022;233(9):780–786. doi: 10.1038/s41415-022-5166-x - DOI - PMC - PubMed
    1. Ghiani L, Chiocca S.. High risk-human papillomavirus in HNSCC: present and future challenges for epigenetic therapies. Int J Mol Sci. 2022;23(7):3483. doi: 10.3390/ijms23073483 - DOI - PMC - PubMed
    1. Hashibe M, Brennan P, Chuang SC, et al. Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the international head and neck cancer epidemiology consortium. Cancer Epidemiol Biomarkers Prev. 2009;18(2):541–550. doi: 10.1158/1055-9965.EPI-08-0347 - DOI - PMC - PubMed
    1. Powell SF, Vu L, Spanos WC, et al. The key differences between human papillomavirus-positive and -negative head and neck cancers: biological and clinical implications. Cancers (Basel). 2021;13(20):5206. doi: 10.3390/cancers13205206 - DOI - PMC - PubMed
    1. Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35. doi: 10.1056/NEJMoa0912217 - DOI - PMC - PubMed

Publication types

MeSH terms

Substances

Associated data

LinkOut - more resources