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

NCT07812467 | Not Yet Recruiting Phase 2

• 1 other identifier: B2026-377R
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Oral Squamous Cell Carcinoma (OSCC); Oropharyngeal Squamous Cell Carcinoma (OPSCC)

Keywords

Rimegepant; Neoadjuvant Chemoimmunotherapy; CGRP Receptor Antagonist; Calcitonin Gene-Related Peptide; Major Pathological Response; Tislelizumab; Nab-Paclitaxel; Cisplatin

Outcome Measures

Primary Outcomes (1)

• Major Pathological Response Rate

  Percentage of participants with 10% or less residual viable tumor cells in the resected primary or recurrent tumor specimen after neoadjuvant treatment. For the randomized efficacy analysis, participants who do not undergo surgery or whose surgical specimens are not evaluable for pathological response will be considered not to have achieved major pathological response. Results will also be reported separately for participants with primary and recurrent disease.

  At pathological assessment of the definitive surgical specimen after completion of two 3-week cycles of neoadjuvant treatment

Secondary Outcomes (7)

• Pathological Complete Response Rate

  At pathological assessment of the definitive surgical specimen after completion of two 3-week cycles of neoadjuvant treatment

• Objective Response Rate

  From baseline to preoperative radiographic assessment after completion of two 3-week cycles of neoadjuvant treatment

• Event-Free Survival

  From randomization to the first event or censoring, assessed up to 5 years

• Overall Survival

  From randomization until death or censoring, assessed up to 5 years

• Change From Baseline in Pain Score

  At baseline, at the end of each neoadjuvant treatment cycle, and at the preoperative assessment

Other Outcomes (3)

• Change From Baseline in Peripheral Blood Immune Cell Subset Proportions Assessed by Multiparameter Flow Cytometry

  At baseline; at the end of Cycle 1 (Day 21); at the end of Cycle 2 (Day 42); and on the day of definitive surgery before anesthesia

• Change From Baseline in Tumor-Infiltrating Immune Cell Subset Proportions Assessed by Single-Cell RNA Sequencing

  At baseline, using the pretreatment biopsy obtained before Cycle 1, and at definitive surgery after completion of two 21-day cycles of neoadjuvant treatment

• CGRP Pathway Biomarkers

  At baseline, using peripheral blood and the pretreatment tumor biopsy obtained before Cycle 1, and at definitive surgery after completion of two 21-day cycles of neoadjuvant treatment

Study Arms (3)

Safety Run-In Combination Arm

EXPERIMENTAL

Twenty participants will receive rimegepant plus standard neoadjuvant chemoimmunotherapy for two 3-week cycles, followed by definitive or intended curative surgery. Safety and tolerability will be evaluated before initiation of the randomized stage.

Drug: Rimegepant; Drug: Tislelizumab; Drug: Nab-paclitaxel; Drug: Cisplatin

Randomized Combination Arm

EXPERIMENTAL

Participants randomized to this arm will receive rimegepant plus standard neoadjuvant chemoimmunotherapy for two 3-week cycles, followed by definitive or intended curative surgery.

Drug: Rimegepant; Drug: Tislelizumab; Drug: Nab-paclitaxel; Drug: Cisplatin

Randomized Control Arm

ACTIVE COMPARATOR

Participants randomized to this arm will receive standard neoadjuvant chemoimmunotherapy alone for two 3-week cycles, followed by definitive or intended curative surgery.

Drug: Tislelizumab; Drug: Nab-paclitaxel; Drug: Cisplatin

Interventions

Rimegepant DRUG

Rimegepant 75 mg will be administered orally every other day from the initiation until the completion of neoadjuvant chemoimmunotherapy.

Randomized Combination Arm; Safety Run-In Combination Arm

Tislelizumab DRUG

Tislelizumab 200 mg will be administered by intravenous infusion on Day 1 of each 3-week treatment cycle for two cycles.

Randomized Combination Arm; Randomized Control Arm; Safety Run-In Combination Arm

Nab-paclitaxel DRUG

Nab-paclitaxel 260 mg/m² will be administered by intravenous infusion on Day 2 of each 3-week treatment cycle for two cycles.

Randomized Combination Arm; Randomized Control Arm; Safety Run-In Combination Arm

Cisplatin DRUG

A total dose of cisplatin 75 mg/m² will be administered intravenously over Days 2 and 3 of each 3-week treatment cycle for two cycles.

Randomized Combination Arm; Randomized Control Arm; Safety Run-In Combination Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead
• Pfizer: collaborator

Study Sites (1)

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

Related Publications (3)

• 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.

  PMID: 41138728 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.

  PMID: 36395769 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.

  PMID: 36323780 BACKGROUND

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

rimegepant sulfate; tislelizumab; 130-nm albumin-bound paclitaxel; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Central Study Contacts

Yu Zhang

CONTACT

+86-13818927554; zhang.yu4@zs-hospital.sh.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study consists of an initial open-label safety run-in stage followed by an open-label randomized parallel-group stage. The safety run-in stage will enroll 20 participants who will receive rimegepant plus standard neoadjuvant chemoimmunotherapy. After the prespecified safety criteria are met, 200 participants will be randomized in a 1:1 ratio to receive rimegepant plus standard neoadjuvant chemoimmunotherapy or standard neoadjuvant chemoimmunotherapy alone. Stratified block randomization will be used in the randomized stage.

Study Record Dates

• First Submitted: July 19, 2026
• First Posted: September 10, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2033
• Last Updated: September 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)