Head and Neck Advanced Research for Multi-Omics and Optimized Immunotherapy

NCT07211139 | Recruiting

• 1 other identifier: 2025-04-059
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Head and neck squamous cell carcinoma is a heterogeneous cancer with varying prognoses depending on anatomical location and characteristics, and advanced cancers have a poor prognosis. This study aimed to examine changes in the tumor microenvironment and systemic immune system before and after combination therapy with immune checkpoint inhibitors, the standard first-line treatment for head and neck cancer. The rationale for this research and development project is as follows:

1. 1.While immune checkpoint inhibitors have improved survival rates for head and neck cancer patients, they are only effective in approximately 15% of patients. Because biomarkers predicting treatment response have not yet been clearly identified, targeting target patient populations is challenging.
2. 2.While numerous studies have examined the tumor microenvironment in head and neck cancer, no studies have spatially compared dynamic changes before and after immune checkpoint inhibitor treatment using paired tissue and blood biopsies. Therefore, the specific treatment mechanisms remain unclear.
3. 3.Little is known about how changes in the tumor microenvironment are reflected in the peripheral blood, making noninvasive treatment response monitoring difficult.
4. 4.Immune checkpoint inhibitor treatment is known to enhance the efficacy of subsequent taxane-based chemotherapy, but the mechanism remains unknown.

Conditions

Head and Neck Cancer

Keywords

Head and Neck Cancer

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS)

  Time from initiation of treatment to death from any cause. Estimated using Kaplan-Meier survival analysis. The effect of clinical and treatment variables on survival will be evaluated using the Cox proportional hazards model.

  Up to 3 years after enrollment.

• Treatment Response

  Tumor response evaluated according to RECIST v1.1 criteria (Complete Response, Partial Response, Stable Disease, Progressive Disease).

  From treatment initiation until disease progression or death, whichever occurs first, assessed every 6-12 weeks, up to 36 months.

Secondary Outcomes (3)

• Progression-Free Survival (PFS)

  Time Frame: Up to 3 years after enrollment.

• Treatment Toxicity

  From first dose of study treatment until 90 days after the last dose of study treatment, up to 36 months.

• Between Clinical/Immunologic Variables and Treatment Outcomes

  Up to 3 years after enrollment.

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with recurrent or metastatic head and neck squamous cell carcinoma treated at Samsung Medical Center. Approximately 600 patients with head and neck cancer visit the center annually, and more than 50 patients are newly diagnosed with recurrent/metastatic disease and receive systemic therapy each year. This study will recruit eligible patients from this population.

You may qualify if:

• Histologically confirmed recurrent/metastatic head and neck squamous cell carcinoma (HNSCC)
• Received first-line combination therapy with immune checkpoint inhibitor and cytotoxic chemotherapy
• Availability of tumor tissue samples at Samsung Medical Center
• p16 and PD-L1 expression status evaluable within the institution
• Age ≥ 20 years
• Ability to understand the study purpose and provide written informed consent

You may not qualify if:

• Considered ineligible for enrollment at the discretion of the investigator

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical Center

Seoul, Seoul, 06351, South Korea

RECRUITING

Related Publications (16)

• Braakhuis BJ, Graveland AP, Dijk F, Ylstra B, van Wieringen WN, Leemans CR, Brakenhoff RH. Expression signature in peripheral blood cells for molecular diagnosis of head and neck squamous cell carcinoma. Oral Dis. 2013 Jul;19(5):452-5. doi: 10.1111/odi.12019. Epub 2012 Oct 3.

  PMID: 23034102 BACKGROUND

• Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Hong RL, Gonzalez Mendoza R, Roy A, Zhang Y, Gumuscu B, Cheng JD, Jin F, Rischin D; KEYNOTE-048 Investigators. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019 Nov 23;394(10212):1915-1928. doi: 10.1016/S0140-6736(19)32591-7. Epub 2019 Nov 1.

  PMID: 31679945 BACKGROUND

• Fang R, Chen Y, Huang B, Wang Z, Zhu X, Liu D, Sun W, Chen L, Zhang M, Lyu K, Lei W. Predicting response to PD-1 inhibitors in head and neck squamous cell carcinomas using peripheral blood inflammatory markers. Transl Oncol. 2025 Jan;51:102222. doi: 10.1016/j.tranon.2024.102222. Epub 2024 Dec 1.

  PMID: 39616985 BACKGROUND

• Harrington KJ, Burtness B, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Brana I, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Lin J, Gumuscu B, Swaby RF, Rischin D. Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. J Clin Oncol. 2023 Feb 1;41(4):790-802. doi: 10.1200/JCO.21.02508. Epub 2022 Oct 11.

  PMID: 36219809 BACKGROUND

• Idel C, Fleckner J, Plotze-Martin K, Werner L, Rades D, Theodoraki MN, Hofmann L, Huber D, Leichtle A, Hoffmann TK, Bruchhage KL, Pries R. Partial recovery of peripheral blood monocyte subsets in head and neck squamous cell carcinoma patients upon radio(chemo)therapy is associated with decreased plasma CXCL11. BMC Cancer. 2024 Apr 12;24(1):459. doi: 10.1186/s12885-024-12177-x.

  PMID: 38609887 BACKGROUND

• Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992 Nov;11(11):3887-95. doi: 10.1002/j.1460-2075.1992.tb05481.x.

  PMID: 1396582 BACKGROUND

• Iwasa YI, Nakajima T, Hori K, Yokota Y, Kitoh R, Uehara T, Takumi Y. A Spatial Transcriptome Reveals Changes in Tumor and Tumor Microenvironment in Oral Cancer with Acquired Resistance to Immunotherapy. Biomolecules. 2023 Nov 22;13(12):1685. doi: 10.3390/biom13121685.

  PMID: 38136558 BACKGROUND

• Jung YS, Lee D, Jung KW, Cho H. Long-term Survivorship and Non-cancer Competing Mortality in Head and Neck Cancer: A Nationwide Population-Based Study in South Korea. Cancer Res Treat. 2023 Jan;55(1):50-60. doi: 10.4143/crt.2021.1086. Epub 2022 Mar 4.

  PMID: 35698446 BACKGROUND

• Jung YS, Seok J, Hong S, Ryu CH, Ryu J, Jung KW. The emergence of oral cavity cancer and the stabilization of oropharyngeal cancer: Recent contrasting epidemics in the South Korean population. Cancer. 2021 May 15;127(10):1638-1647. doi: 10.1002/cncr.33434. Epub 2021 Feb 17.

  PMID: 33595858 BACKGROUND

• Kim DH, Kang M, Park G, Mostafavi M, Lim Y, Ock CY, Koh J, Jeon YK, Jung KC, Ahn SH, Chung EJ, Kwon SK, Keam B. Changes in the tumor microenvironment in recurrent head and neck squamous cell carcinoma and its implication on efficacy of immune checkpoint inhibitors. Discov Oncol. 2024 Nov 20;15(1):686. doi: 10.1007/s12672-024-01504-0.

  PMID: 39567471 BACKGROUND

• Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996 Mar 22;271(5256):1734-6. doi: 10.1126/science.271.5256.1734.

  PMID: 8596936 BACKGROUND

• Lin X, Zhao X, Chen Y, Yang R, Dai Z, Li W, Lin C, Cao W. CXC ligand 13 orchestrates an immunoactive microenvironment and enhances immunotherapy response in head and neck squamous cell carcinoma. Int J Immunopathol Pharmacol. 2024 Jan-Dec;38:3946320241227312. doi: 10.1177/03946320241227312.

  PMID: 38252495 BACKGROUND

• Muijlwijk T, Nijenhuis DNLM, Ganzevles SH, Ekhlas F, Ballesteros-Merino C, Peferoen LAN, Bloemena E, Fox BA, Poell JB, Leemans CR, Brakenhoff RH, van de Ven R. Immune cell topography of head and neck cancer. J Immunother Cancer. 2024 Jul 24;12(7):e009550. doi: 10.1136/jitc-2024-009550.

  PMID: 39053947 BACKGROUND

• Ouyang M, Sun H, Liu X, Wu H, Deng F, Shen E, Peng G, Wu H, Zhao Y, Xiong H, Liu B, He S, Hu Y, Liu P. The efficacy and safety of a taxane-based chemotherapy regimen combined with a PD-1 inhibitor in HNSCC: a multicenter real-world study. World J Surg Oncol. 2025 Jan 4;23(1):6. doi: 10.1186/s12957-024-03644-7.

  PMID: 39754263 BACKGROUND

• Trellakis S, Farjah H, Bruderek K, Dumitru CA, Hoffmann TK, Lang S, Brandau S. Peripheral blood neutrophil granulocytes from patients with head and neck squamous cell carcinoma functionally differ from their counterparts in healthy donors. Int J Immunopathol Pharmacol. 2011 Jul-Sep;24(3):683-93. doi: 10.1177/039463201102400314.

  PMID: 21978700 BACKGROUND

• Yu Y, Zakeri K, Sherman EJ, Lee NY. Association of Low and Intermediate Combined Positive Scores With Outcomes of Treatment With Pembrolizumab in Patients With Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma: Secondary Analysis of Keynote 048. JAMA Oncol. 2022 Aug 1;8(8):1216-1218. doi: 10.1001/jamaoncol.2022.1846.

  PMID: 35679031 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Biospecimen Description: Tumor tissue and peripheral blood samples will be collected for translational research. Tumor tissue: Paired biopsies will be obtained from lesions identified by medical oncologists and otolaryngologists. Sampling will occur before treatment, after one cycle (3 ± 1 weeks), and, if feasible, at disease progression. Fresh frozen tissue will be prioritized; if unavailable, formalin-fixed paraffin-embedded (FFPE) tissue will be used. Peripheral blood: 20-30 mL will be collected at baseline, 3, 6, and 12 weeks after treatment initiation, during radiologic assessments, and at disease progression. Each participant will have at least six blood draws. Stored sample types: Fresh frozen tumor tissue, FFPE tissue, whole blood, plasma, serum, and peripheral blood mononuclear cells (PBMCs). All biospecimens will be stored under controlled conditions for immunologic, genomic, and molecular analyses.

MeSH Terms

Conditions

Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Central Study Contacts

Jinyoung Kim, M.D.

CONTACT

+821066576474; lisakjy@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Clinical Professor, Department of Oncology, Samsung Medical Center

Study Record Dates

• First Submitted: September 17, 2025
• First Posted: October 7, 2025
• Study Start: July 8, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: October 7, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)