Rimegepant-Sensitized Neoadjuvant Chemoimmunotherapy for Oral or Oropharyngeal Squamous Cell Carcinoma

Summary

This study will evaluate whether adding rimegepant to standard neoadjuvant chemoimmunotherapy can improve treatment response in patients with primary or recurrent oral or oropharyngeal squamous cell carcinoma who are planned to undergo surgery. Rimegepant blocks the receptor for calcitonin gene-related peptide, also known as CGRP. CGRP signaling may affect the tumor immune environment and the response of tumors to anticancer treatment. The study includes an initial safety run-in stage involving 20 participants, followed by a randomized controlled stage involving 200 participants. During the randomized stage, participants will be assigned in a 1:1 ratio to receive standard neoadjuvant chemoimmunotherapy either with or without rimegepant. All participants will receive two cycles of neoadjuvant treatment followed by definitive or intended curative surgery. The main outcome is the major pathological response rate, defined as 10% or less residual viable tumor in the surgical specimen. Other outcomes include pathological complete response, objective response, event-free survival, overall survival, changes in pain and quality of life, and treatment safety.

Timeline

Start

2026-10-01

Primary completion

2028-10-31

Completion

2033-10-31

Publications

• Background Zhang Y, Guo Y, Liu Z, Sun Y, Yang X, Chen M, Feng G, Lin C, Wang Y, Zhang Z, Zhu Y, Ye J, Liu J, Shi J, Zhou X, Han Q, Liu Y, Jiang Q, Yu Y, Wang X, Zhang C, Sun Y, Zhou J, Fan J, Ji T. Cancer cells co-opt an inter-organ neuroimmune circuit to escape immune surveillance. Cell. 2025 Nov 26;188(24):6754-6773.e29. doi: 10.1016/j.cell.2025.09.029. Epub 2025 Oct 24.
• Background Zhang Y, Lin C, Liu Z, Sun Y, Chen M, Guo Y, Liu W, Zhang C, Chen W, Sun J, Xia R, Hu Y, Yang X, Li J, Zhang Z, Cao W, Sun S, Wang X, Ji T. Cancer cells co-opt nociceptive nerves to thrive in nutrient-poor environments and upon nutrient-starvation therapies. Cell Metab. 2022 Dec 6;34(12):1999-2017.e10. doi: 10.1016/j.cmet.2022.10.012. Epub 2022 Nov 16.
• Background Balood M, Ahmadi M, Eichwald T, Ahmadi A, Majdoubi A, Roversi K, Roversi K, Lucido CT, Restaino AC, Huang S, Ji L, Huang KC, Semerena E, Thomas SC, Trevino AE, Merrison H, Parrin A, Doyle B, Vermeer DW, Spanos WC, Williamson CS, Seehus CR, Foster SL, Dai H, Shu CJ, Rangachari M, Thibodeau J, V Del Rincon S, Drapkin R, Rafei M, Ghasemlou N, Vermeer PD, Woolf CJ, Talbot S. Nociceptor neurons affect cancer immunosurveillance. Nature. 2022 Nov;611(7935):405-412. doi: 10.1038/s41586-022-05374-w. Epub 2022 Nov 2.

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