A Study for Identification of Immune Determinants for Response to Nivolumab in Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

NCT04603248 | Completed

• 1 other identifier: 4-2020-0801
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

A study for identification of immune determinants for response to Nivolumab in Recurrent /Metastatic HNSCC(Head and neck squamous cell carcinoma) patients. Recurrent and metastatic head and neck squamous cell carcinoma is incurable and requires aggressive treatment, resulting in functional disability, dismal prognosis, and high mortality rate. Prognosis of Recurrent and metastatic head and neck squamous cell carcinoma is poor, with limited treatment options and survival rates of 6-9 months following standard-of-care (SOC) therapies. Clinical trials have demonstrated promising clinical activity of anti PD-1(programmed death-1) therapy in head and neck squamous cell carcinoma. Currently, nivolumab were approved for head and neck squamous cell carcinoma refractory to platinum-based therapy. However, the response rate of anti PD-1(programmed death-1) therapy is relatively low and durable clinical benefit is limited to the minority of patients. Moreover, the presence of PD-1(programmed death-1) did not clearly predict response and treatment survival outcome, reflecting imperfection of this biomarker. Actually, PD-1(programmed death-1) negativity cannot preclude the therapeutic benefit of PD-1(programmed death-1) blockade, and vice versa. Hence, development of reliable predictive biomarkers is essential for proper patient selection to maximize clinical benefit of PD-1(programmed death-1) blockade in head and neck squamous cell carcinoma patients. Therefore, we need to select patients who are most likely to benefit from anti PD-1(programmed death-1) therapy and identify the better biomarker to predict the response to PD-1(programmed death-1) blockade in head and neck squamous cell carcinoma patients. patients earlier than tumor assessment by imaging scan. In the current study, we aimed to elucidate immune-related biomarkers to predict response with tumor tissue and peripheral blood from Recurrent /Metastatic HNSCC(Head and neck squamous cell carcinoma) patients treated with nivolumab.

Conditions

Head and Neck Squamous Cell Carcinoma (HNSCC)

Keywords

Head and Neck Squamous Cell Carcinoma (HNSCC)

Outcome Measures

Primary Outcomes (9)

• Explore the biomarkers to predict objective response (OR)

  Single cell RNA sequencing (scRNA-seq), Multiplex IHC (Vectra Polaris®), T cell immunophenotyping using flow cytometry, papilloma virus (HPV) infection status with p16 immunohistochemistry or HPV in-situ hybridization, Microbiome, Evaluation of PD-L1 expression status based on combined positivity score and tumor rate score

  Screening

• Explore the biomarkers to predict objective response (OR)

  Single cell RNA sequencing (scRNA-seq), Multiplex IHC (Vectra Polaris®), T cell immunophenotyping using flow cytometry, papilloma virus (HPV) infection status with p16 immunohistochemistry or HPV in-situ hybridization, Evaluation of PD-L1 expression status based on combined positivity score and tumor rate score

  Before Cycle2 Day1 (each cycle is 14 days)

• Explore the biomarkers to predict objective response (OR)

  Single cell RNA sequencing (scRNA-seq), Multiplex IHC (Vectra Polaris®), T cell immunophenotyping using flow cytometry, papilloma virus (HPV) infection status with p16 immunohistochemistry or HPV in-situ hybridization, Evaluation of PD-L1 expression status based on combined positivity score and tumor rate score

  From date of randomization until the date of first documented progression or date of unacceptable toxicity, whichever came first, assessed up to 100 months

• Explore the biomarkers to predict progression-free survival (PFS)

  Single cell RNA sequencing (scRNA-seq), Multiplex IHC (Vectra Polaris®), T cell immunophenotyping using flow cytometry, papilloma virus (HPV) infection status with p16 immunohistochemistry or HPV in-situ hybridization, Microbiome, Evaluation of PD-L1 expression status based on combined positivity score and tumor rate score

  Screening

• Explore the biomarkers to predict progression-free survival (PFS)

  Single cell RNA sequencing (scRNA-seq), Multiplex IHC (Vectra Polaris®), T cell immunophenotyping using flow cytometry, papilloma virus (HPV) infection status with p16 immunohistochemistry or HPV in-situ hybridization, Evaluation of PD-L1 expression status based on combined positivity score and tumor rate score

  Before Cycle2 Day1 (each cycle is 14 days)

• Explore the biomarkers to predict progression-free survival (PFS)

  Single cell RNA sequencing (scRNA-seq), Multiplex IHC (Vectra Polaris®), T cell immunophenotyping using flow cytometry, papilloma virus (HPV) infection status with p16 immunohistochemistry or HPV in-situ hybridization, Evaluation of PD-L1 expression status based on combined positivity score and tumor rate score

  From date of randomization until the date of first documented progression or date of unacceptable toxicity, whichever came first, assessed up to 100 months

• Explore the biomarkers to predict overall survival (OS)

  Single cell RNA sequencing (scRNA-seq), Multiplex IHC (Vectra Polaris®), T cell immunophenotyping using flow cytometry, papilloma virus (HPV) infection status with p16 immunohistochemistry or HPV in-situ hybridization, Microbiome, Evaluation of PD-L1 expression status based on combined positivity score and tumor rate score

  Screening

• Explore the biomarkers to predict overall survival (OS)

  Single cell RNA sequencing (scRNA-seq), Multiplex IHC (Vectra Polaris®), T cell immunophenotyping using flow cytometry, papilloma virus (HPV) infection status with p16 immunohistochemistry or HPV in-situ hybridization, Evaluation of PD-L1 expression status based on combined positivity score and tumor rate score

  Before Cycle2 Day1 (each cycle is 14 days)

• Explore the biomarkers to predict overall survival (OS)

  Single cell RNA sequencing (scRNA-seq), Multiplex IHC (Vectra Polaris®), T cell immunophenotyping using flow cytometry, papilloma virus (HPV) infection status with p16 immunohistochemistry or HPV in-situ hybridization, Evaluation of PD-L1 expression status based on combined positivity score and tumor rate score

  From date of randomization until the date of first documented progression or date of unacceptable toxicity, whichever came first, assessed up to 100 months

Secondary Outcomes (1)

• Safety: Number of participants with adverse events and abnormal laboratory values as assessed by NCI-CTCAE version 5

  From date of randomization until the date of first documented progression or date of unacceptable toxicity, whichever came first, assessed up to 100 months

Study Arms (1)

Single Arm

EXPERIMENTAL

Drug: Nivolumab

Interventions

Nivolumab DRUG

Nivolumab 3mg/kg treatment will be given every 2 weeks up to progression or unacceptable toxicity

Single Arm

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sex: Male or female
• Age (at the time of informed consent): 19 years and older
• Subjects with histologically- or cytologically-confirmed recurrent and/or metastatic head and neck squamous cell carcinoma (Recurrent/Metastatic HNSCC)
• Known human papilloma virus (HPV) infection status with p16 immunohistochemistry or HPV in-situ hybridization
• Failed or intolerable to previous platinum-based chemotherapy
• Patients who have at least 1 measurable or non-measurable lesion per the RECIST (Response Evaluation Criteria in Solid Tumor) Guideline Ver. 1.1 as confirmed by imaging within 28 days before enrollment. The following requirements should also be satisfied:
• If patients only have lesions that were previously treated with radiation, the lesion should be limited to one with confirmed aggravation by imaging after radiation.
• If patients have pericardial or pleural effusion or ascites only, the lesion should be limited to one with cytologically confirmed malignancy.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Patients with a life expectancy of at least 3 months
• Screening laboratory values within the specified ranges stated below, obtained within 14 days prior to first dose:
• White blood cells ≥2,000/mm3 and neutrophils ≥1,500/mm3
• Platelets ≥100,000/mm3
• Hemoglobin ≥9.0 g/dL
• AST (GOT) and ALT (GPT) ≤3.0-fold the upper limit of normal (ULN) of the study site (or ≤5.0-fold the ULN of the study site in patients with liver metastases)

You may not qualify if:

• Patients with multiple primary cancers (with the exception of completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma, or superficial bladder cancer, or any other cancer that has not recurred for at least 3 years)
• Patients with residual adverse effects of prior therapy or effects of surgery that would affect the safety evaluation of the investigational product in the opinion of the investigator or sub-investigator.
• Patients with current or past history of severe hypersensitivity to any other antibody products
• Patients with concurrent autoimmune disease or history of chronic or recurrent autoimmune disease
• Patients with a current or past history of interstitial lung disease or pulmonary fibrosis diagnosed based on imaging or clinical findings. Patients with radiation pneumonitis may be enrolled if the radiation pneumonitis has been confirmed as stable (beyond acute phase) without any concerns about recurrence.
• Patients with concurrent diverticulitis or symptomatic gastrointestinal ulcerative disease
• Patients with any metastasis in the brain or meninx that is symptomatic or requires treatment. Patients may be enrolled if the metastasis is asymptomatic and requires no treatment.
• Patients with pericardial fluid, pleural effusion, or ascites requiring treatment
• Patients with uncontrollable, tumor-related pain
• Patients who have experienced medically refractory transient ischemic attack, cerebrovascular accident, thrombosis, or thromboembolism (pulmonary arterial embolism or deep vein thrombosis) within 180 days before enrollment
• Patients with a history of uncontrollable or significant cardiovascular disease meeting any of the following criteria:
• Myocardial infarction within 180 days before enrollment
• Uncontrollable angina pectoris within 180 days before enrollment
• New York Heart Association (NYHA) Class III or IV congestive heart failure
• Uncontrollable hypertension despite appropriate treatment (e.g., systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥ 90 mmHg lasting 24 hours or more)

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei Severance Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Nivolumab

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Hye Ryun Kim

  Severance Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 8, 2020
• First Posted: October 26, 2020
• Study Start: December 3, 2020
• Primary Completion: March 18, 2026
• Study Completion: March 18, 2026
• Last Updated: June 10, 2026

Record last verified: 2026-06

Locations

KR (1)