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

A Phase II Randomized Controlled Clinical Trial of Rimegepant-Sensitized Neoadjuvant Chemoimmunotherapy in Patients With Oral/Oropharyngeal Squamous Cell Carcinoma

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.

Inclusion Criteria:

• Age 18 to 75 years, regardless of sex.
• Histologically or cytologically confirmed oral or oropharyngeal squamous cell carcinoma, including primary disease or recurrent disease after previous treatment that is considered amenable to repeat curative-intent resection.
• Planned to receive neoadjuvant chemoimmunotherapy followed by surgery after multidisciplinary evaluation.
• At least one evaluable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Adequate major organ function.
• Voluntary participation and provision of written informed consent.

Exclusion Criteria:

• Severe cardiac, hepatic, or renal dysfunction.
• Active autoimmune disease.
• Pregnancy or breastfeeding.
• Known allergy or hypersensitivity to rimegepant or any component of the planned neoadjuvant treatment.
• Any condition that, in the investigator's judgment, makes the participant unsuitable for enrollment.