Head and Neck Advanced Research for Multi-Omics and Optimized Immunotherapy(HARMONI)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
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:
- 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.
- 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.
- Little is known about how changes in the tumor microenvironment are reflected in the peripheral blood, making noninvasive treatment response monitoring difficult.
- Immune checkpoint inhibitor treatment is known to enhance the efficacy of subsequent taxane-based chemotherapy, but the mechanism remains unknown.
Therefore, we aim to explore biomarkers that predict treatment response to combination therapy with immune checkpoint inhibitors and cytotoxic chemotherapy in patients with advanced/metastatic head and neck cancer and develop personalized treatment strategies.
详细描述
1. Background 1.1 Research Background Immune checkpoint inhibitors (ICIs) have emerged as a new class of anticancer therapy following cytotoxic chemotherapy and targeted therapy. They have demonstrated survival benefits in various solid tumors, including head and neck cancers, thereby shifting the paradigm of cancer treatment. Tumors evade immune surveillance through checkpoint molecules such as PD-1 and CTLA-4, and the development of ICIs such as pembrolizumab and nivolumab has shown efficacy in head and neck cancers as well.
Advanced and metastatic head and neck cancers not only pose life-threatening risks but also severely affect speech, swallowing, and appearance, leading to a higher suicide rate compared to the general population. In Korea, the incidence of head and neck cancer increased by about 30% between 2010 and 2020, with tongue cancer showing a particularly steep rise of 7.7% per year in young adults aged 20-30.
In the KEYNOTE-048 trial, pembrolizumab combined with platinum-based chemotherapy significantly prolonged overall survival compared to cetuximab-based regimens, with greater benefit observed in patients with PD-L1 CPS ≥20 or ≥1. Subsequent analyses showed that the survival benefit correlated with PD-L1 CPS only in the pembrolizumab-combination group, and about 20% of patients were identified as long responders. However, the overall response rate to ICIs remains only 15-26%, and PD-L1 CPS alone does not fully explain treatment outcomes.
The TIME (tumor immune microenvironment) study on head and neck cancer classified tumors into fully infiltrated, stroma-restricted, immune-excluded, and immune-desert subtypes, with 48% being fully infiltrated. Tumors with high expression of cytokines such as CXCL13, IFN-γ, and IL-10 exhibited more active immune cell infiltration. However, these results were based on pre-treatment tissues, and there is a lack of studies investigating TIME changes after treatment.
In recurrent head and neck cancer, intratumoral and stromal TIL density significantly decreased, while the proportion of immune-desert tumors increased. Stromal TIL enrichment correlated with better response to ICIs. However, this study was based on AI-driven image analysis and did not capture detailed immune microenvironment composition or post-treatment dynamics.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Not meeting the inclusion criteria
- •Considered ineligible for enrollment at the discretion of the investigator
结局指标
主要结局
Overall Survival (OS)
时间窗: Up to 3 years after enrollment.
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.
Treatment Response
时间窗: From treatment initiation until disease progression or death, whichever occurs first, assessed every 6-12 weeks, up to 36 months.
Tumor response evaluated according to RECIST v1.1 criteria (Complete Response, Partial Response, Stable Disease, Progressive Disease).
次要结局
- 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.)
研究者
JinYong Kim
Assistant Clinical Professor, Department of Oncology, Samsung Medical Center
Samsung Medical Center