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

NCT04080804 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: HCC 18-139CA224-056
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Head and Neck Squamous Cell Carcinoma (HNSCC)

Keywords

anti-PD1 antibody; anti-CTLA4 antibody; anti-LAG3 antibody; tumor infiltrating lymphocyte (TIL)

Outcome Measures

Primary Outcomes (4)

• Adverse Events related to treatment of nivolumab in combination with relatlimab

  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.

  Up to 4 months

• Adverse Events related to treatment of nivolumab in combination with ipilimumab

  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.

  Up to 4 months

• Objective Response Rate (ORR)

  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.

  Up to 4 months

• Pathologic Response Rate

  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.

  Up to 4 months

Secondary Outcomes (4)

• Levels of tumor infiltrating lymphocyte (TIL) subsets

  Up to 6 months (prior to the first day of treatment, on Days 1 and 28 of treatment, day of surgery, 1, 3, 6 months post surgery)

• Levels of peripheral blood lymphocytes (PBL)

  Up to 6 months (prior to the first day of treatment, on Days 1 and 28 of treatment, day of surgery, 1, 3, 6 months post surgery)

• Effector CD4+ cells

  Up to 6 months (prior to the first day of treatment, on Days 1 and 28 of treatment, day of surgery, 1, 3, 6 months post surgery)

• Effector CD8+ cells

  Up to 6 months (prior to the first day of treatment, on Days 1 and 28 of treatment, day of surgery, 1, 3, 6 months post surgery)

Other Outcomes (3)

• Tumor mutational burden

  Up to 2 months (prior to treatment and day of surgery)

• Gene expression signature

  Up to 2 months (prior to treatment and day of surgery)

• Single cell RNAseq pathways

  Up to 2 months (prior to treatment and day of surgery)

Study Arms (2)

Nivolumab + Relatlimab

EXPERIMENTAL

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

Drug: Nivolumab; Drug: Relatlimab

Nivolumab + Ipilimumab

EXPERIMENTAL

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)

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

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.

Also known as: anti-PD-1 antibody, OPDIVO®

Nivolumab + Ipilimumab; Nivolumab + Relatlimab

Relatlimab DRUG

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

Also known as: anti-LAG3 antibody, BMS-986016

Nivolumab + Relatlimab

Ipilimumab DRUG

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

Also known as: anti-CTLA4 antibody, Yervoy ®

Nivolumab + Ipilimumab

Eligibility Criteria

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

You may qualify if:

• Males and females, ages ≥18 years
• Histologically or cytologically confirmed Squamous Cell Carcinoma, previously untreated stage III, or IVA HNC by AJCC 8th edition staging system. Newly diagnosed, never treated HNC cancer but could have had a surgically treated primary \> 5 years previous without radiotherapy or chemotherapy. For HPV positive oropharyngeal cancer, patients with T3 or T4 primary and/or one ipsilateral lymph node greater than 3 cm, multiple ipsilateral lymph nodes, bilateral lymph nodes, or contralateral lymph node will be included. Patients must undergo CT or MRI to rule out the presence of distant metastases.
• Accessible tumor for pretreatment (baseline) open/incisional biopsy to provide adequate correlative specimen.
• Have LAG-3 and PD-L1 results for stratification.
• LVEF assessment with documented LVEF ≥50% by either TTE or MUGA (TTE preferred test) within 28 days prior to first study drug administration
• Women of child-bearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. All WOCBP MUST have a negative pregnancy test within 7 days prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study. All WOCBP must agree to use appropriate contraception to prevent pregnancy for the duration of treatment with study treatments, plus 24 weeks after the last dose of study treatment (i.e., 30 days \[duration of ovulatory cycle\] plus approximately 5 half-lives).
• All males must agree to use appropriate contraception for the duration of treatment with study treatments plus 33 weeks after the last dose of study treatment (i.e., 90 days \[duration of sperm turnover\] plus approximately 5 half-lives). In addition, male participants must be willing to refrain from sperm donation during this time. In addition, men enrolled on this study must be informed of the risks to any sexual partner of childbearing potential and should practice an effective method of birth control
• Azoospermic males are exempt from contraceptive requirements unless the potential exists for fetal toxicity due to study drug being present in seminal fluid, even if the participant has undergone a successful vasectomy or if the partner is pregnant. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, and still must undergo pregnancy testing as described in this section.
• Primary tumors of the oral cavity, oropharynx, hypopharynx, or larynx will be included.
• Eligible for surgical resection.
• Age ≥ 18 years
• ECOG performance status 0-1.
• Have signed written informed consent

You may not qualify if:

• Prior radiation, chemotherapy, oncology vaccine or immunotherapy.
• Prior severe infusion reaction to a monoclonal antibody.
• Troponin T (TnT) or I (TnI) \> 2 × institutional ULN. Subjects with TnT or TnI levels between \> 1 to 2 × ULN will be permitted if repeat levels within 24 hours are less than or equal to 1 x ULN. If TnT or TnI levels are \> 1 to 2 × ULN within 24 hours, the subject may undergo a cardiac evaluation and be considered for treatment, following a discussion with the BMS Medical Monitor or designee. When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT or TnI repeat levels beyond 24 hours are \< 2 x ULN, the subject may undergo a cardiac evaluation and be considered for treatment.
• Evidence of distant metastasis.
• Prior history of HNC treated \< 5 years previously.
• Prior history of myocarditis, regardless of etiology
• Prior treatment with LAG-3 targeted agents.
• A known history of Hepatitis B or C
• Patients with active/history of autoimmune disease. "Active" refers to any condition currently requiring therapy. Examples of autoimmune disease include systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease and rheumatoid arthritis
• Psychiatric illness or other social issues limiting compliance
• If second primary tumor is found at the time of EUA, the subject will be excluded from study participation.

Sponsors & Collaborators

• Dan Zandberg: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Nivolumab; spartalizumab; relatlimab; Ipilimumab

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

• Dan Zandberg, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

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

Study Record Dates

• First Submitted: September 3, 2019
• First Posted: September 6, 2019
• Study Start: December 20, 2019
• Primary Completion (Estimated): July 17, 2026
• Study Completion (Estimated): October 17, 2026
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)