Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Nivolumab

Ipilimumab

Relatlimab

Immunoglobulins

Immunoglobulins, Intravenous

Immunologic Factors

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Nivolumab 480mg IV + Relatlimab 480mg IV D1 - optional Nivolumab 480 mg IV + Relatlimab 480mg IV D28 (D28 at clinician discretion i.e. surgery postponed)

Nivolumab 3 mg/kg IV + Ipilimumab 1 mg/kg D1 then Nivolumab 3 mg /kg D14 and then optional Nivolumab 3 mg/kg D28 (D28 at clinician discretion i.e., surgery postponed)

A fully human anti-programmed death 1 (PD-1) monoclonal antibody checkpoint inhibitor, that blocks a signal that prevents activated T cells from attacking the cancer cells.

A monoclonal antibody with anti-Lymphocyte-activation gene 3 (LAG-3) (immune checkpoint receptor protein found on the cell surface) activity.

A monoclonal anitibody that targets CTLA-4, a protein receptor, that down regulates the immune system.

Jennifer Ruth, RN, BSN

Rosemarie Angelo, RN, BSN

Robert L Ferris, MD, PhD

Robert Ferris, MD, PhD

The aim of this study is to potentiate adaptive immunity to enhance the anti-tumor activity of anti-PD1 antibody by the addition of anti-CTLA4 antibody or anti-LAG3 antibody (relatlimab) given in subjects with resectable locally advanced HNSCC prior to surgical resection.

Immunotherapeutic agents have been well tolerated in the recurrent/metastatic patient population. Studies have shown that delay of surgical resection for 3-4 weeks after diagnosis is acceptable. Overall survival for locally advanced head and neck squamous cell carcinoma are poor with the current treatment modalities available. Previously untreated, locally advanced (AJCC 8th edition stage III-IVa) HPV+ and HPV- head and neck squamous cell carcinoma patients who are candidates for surgical resection, as deemed by the multidisciplinary team will be included in this trial. Patients with histories of autoimmune disease or with current or previous histories of immune modulating agents will be excluded from participation.

Relatlimab will be given IV at a dose of 480 mg IV on D1 (and on D28 if surgery is postponed at the discretion of the investigator). Nivolumab will be given IV at a dose of 480 mg on D1 (and on D28 if surgery is postponed at the discretion of the investigator) when given alone or with relatlimab. Nivolumab will be given at dose of 3 mg/kg IV every 2 weeks on D1 and D14 (and on D28 if the operating room time is not yet available, and the 4-week CT scan demonstrates at least stable disease ) when given with Ipilimumab. Ipilimumab will be given at a dose of 1 mg/kg IV once only on D1. Patients will undergo biopsy and CT scan prior to treatment initiation. 4 weeks (± 1 week) after, patient will undergo surgical resection. CT scan will be repeated prior to surgery (from 1-72 hours prior to surgery).The patients will be monitored from time of biopsy until 6 months postoperatively.

Stage II-IVa locally advanced (LA) resectable HNSCC; stratified by HPV, LAG-3 and PD-L1 status

Study of Safety and Tolerability of Nivolumab Treatment Alone or in Combination With Relatlimab or Ipilimumab in Head and Neck Cancer

A Phase II Neoadjuvant Study of the Safety and Tolerability of Anti-PD1 (Nivolumab) Administered Alone or in Combination With Anti-LAG3 (Relatlimab) or Anti-CTLA4 (Ipilimumab) in Resectable Head and Neck Cancer

A measurement of mutations carried by tumor cells. It is a predictive biomarker being studied to evaluate its association with response to the study therapy, which may help to plan the best treatment. Tumors that have a high number of mutations appear to be more likely to respond to certain types of immunotherapy.

A single or combined group of genes in a cell with a uniquely characteristic pattern of gene expression that occurs as a result of cancer or other altered or unaltered pathogenic. Gene signature can serve as a prognostic biomarker for the associated disease.

Cellular pathways that examine the sequence information from individual cells with optimized next generation sequencing (NGS) technologies, providing a higher resolution of cellular differences and a better understanding of the function of an individual cell in the context of its microenvironment.

Number of participants experiencing adverse events greater than grade 3 related to treatment with nivolumab in combination with relatlimab per Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Number of participants experiencing adverse events greater than grade 3 related to treatment with nivolumab in combination with ipilimumab per Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Percentage of patients with partial response (PR) or complete response (CR) to the treatment per RECIST 1.1. criteria. v1.1. Per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or nontarget) with reduction in short axis to \<10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Percentage of patients with complete response (CR) to the treatment per RECIST 1.1. criteria. v1.1. Per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or nontarget) with reduction in short axis to \<10 mm.

Levels of tumor infiltrating lymphocyte (TIL) subsets in peripheral blood. Tumor-infiltrating lymphocytes are white blood cells that have left the bloodstream and migrated towards a tumor. The presence of lymphocytes in tumors is often associated with better post-surgical clinical outcomes and after immunotherapy.

Levels of peripheral blood lymphocytes (PBL) in blood. PBL levels may be useful in predicting response to chemotherapy.

Presence of CD4+ cells in tumor tissue at the time of biopsy and resection specimen collection. CD4 T-cell can play a role in the development of tumor immunity.

Presence and level of CD8+ T cells in peripheral blood. CD8-positive T cells are a critical subpopulation of MHC class I-restricted T cell and are mediators of adaptive immunity. They include cytotoxic T cells, which are important for killing cancerous cells.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Safety and Tolerability of Nivolumab Treatment Alone or in Combination With Relatlimab or Ipilimumab in Head and Neck Cancer	NCT04080804	Head and Neck S...	Nivolumab Relatlimab Ipilimumab	18 Years -	University of Pittsburgh
Study of Safety and Tolerability of Nivolumab Treatment Alone or in Combination With Relatlimab or Ipilimumab in Head and Neck Cancer	NCT04080804	Head and Neck S...	Nivolumab Relatlimab Ipilimumab	18 Years -	University of Pittsburgh

Spots Global Cancer Trial Database for tumor infiltrating lymphocyte (til)