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Head and Neck Squamous Cell Carcinoma (HNSCC)Phase 2NCT04080804

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

A Phase 2 study testing Nivolumab, Relatlimab and Ipilimumab in people with Head and Neck Squamous Cell Carcinoma (HNSCC), run by Dan Zandberg at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nivolumab, Relatlimab and Ipilimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
1 siteUnited States
Study dates
20 Dec 2019to 13 Apr 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

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.

Being tested
Nivolumab, Relatlimab, Ipilimumab
Keywords
anti-PD1 antibody, anti-CTLA4 antibody, anti-LAG3 antibody, tumor infiltrating lymphocyte (TIL)
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Also called anti-PD-1 antibody, OPDIVO®

    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.

  • RelatlimabDrug

    Also called anti-LAG3 antibody, BMS-986016

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

  • IpilimumabDrug

    Also called anti-CTLA4 antibody, Yervoy ®

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

Study groups in NCT04080804
Study groupRoleWhat they receive
Nivolumab + RelatlimabExperimentalNivolumab 480mg IV + Relatlimab 480mg IV D1 - optional Nivolumab 480 mg IV + Relatlimab 480mg IV D28 (D28 at clinician discretion i.e. surgery postponed)
Receives: Drug: Nivolumab; Drug: Relatlimab
Nivolumab + IpilimumabExperimentalNivolumab 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)
Receives: Drug: Nivolumab; Drug: Ipilimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 4 months

  2. 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.

    Measured: Up to 4 months

  3. 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.

    Measured: Up to 4 months

  4. 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.

    Measured: Up to 4 months

Secondary outcomes (4)
  1. Levels of tumor infiltrating lymphocyte (TIL) subsets

    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.

    Measured: 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)

  2. Levels of peripheral blood lymphocytes (PBL)

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

    Measured: 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)

  3. Effector CD4+ cells

    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.

    Measured: 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)

  4. Effector CD8+ cells

    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.

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Sep 2019
  2. Study start20 Dec 2019
  3. Primary completion13 Apr 2026
  4. Study completion13 Apr 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Stage II-IVa locally advanced (LA) resectable HNSCC; stratified by HPV, LAG-3 and PD-L1 status
Masking
None (open label)
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04080804
Sponsor's protocol ID
HCC 18-139
Other IDs
CA224-056
Status last verified
Sep 2026
First submitted
3 Sep 2019
Last updated
9 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab, Relatlimab and Ipilimumab in people with Head and Neck Squamous Cell Carcinoma (HNSCC), run by Dan Zandberg at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse Events related to treatment of nivolumab in combination with relatlimab (time frame: Up to 4 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2026.

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