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

NCT ID: NCT04080804

Last Updated: 2024-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-12-20

Study Completion Date

2026-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Head and Neck Squamous Cell Carcinoma (HNSCC)

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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

TREATMENT

Blinding Strategy

NONE

Study Groups

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Nivolumab + Relatlimab

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type 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.

Relatlimab

Intervention Type DRUG

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

Nivolumab + Ipilimumab

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)

Group Type EXPERIMENTAL

Nivolumab

Intervention Type 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.

Ipilimumab

Intervention Type DRUG

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

Interventions

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Nivolumab

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.

Intervention Type DRUG

Relatlimab

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

Intervention Type DRUG

Ipilimumab

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

Intervention Type DRUG

Other Intervention Names

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anti-PD-1 antibody OPDIVO® anti-LAG3 antibody BMS-986016 anti-CTLA4 antibody Yervoy ®

Eligibility Criteria

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Inclusion Criteria

1. Males and females, ages ≥18 years
2. 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.
3. Accessible tumor for pretreatment (baseline) open/incisional biopsy to provide adequate correlative specimen.
4. Have LAG-3 and PD-L1 results for stratification.
5. LVEF assessment with documented LVEF ≥50% by either TTE or MUGA (TTE preferred test) within 28 days prior to first study drug administration
6. 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).
7. 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
8. 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.
9. Primary tumors of the oral cavity, oropharynx, hypopharynx, or larynx will be included.
10. Eligible for surgical resection.
11. Age ≥ 18 years
12. ECOG performance status 0-1.
13. Have signed written informed consent

Exclusion Criteria

1. Prior radiation, chemotherapy, oncology vaccine or immunotherapy.
2. Prior severe infusion reaction to a monoclonal antibody.
3. 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.
4. Evidence of distant metastasis.
5. Prior history of HNC treated \< 5 years previously.
6. Prior history of myocarditis, regardless of etiology
7. Prior treatment with LAG-3 targeted agents.
8. A known history of Hepatitis B or C
9. 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
10. Psychiatric illness or other social issues limiting compliance
11. If second primary tumor is found at the time of EUA, the subject will be excluded from study participation.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Dan Zandberg

OTHER

Sponsor Role lead

Responsible Party

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Dan Zandberg

Associate Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Dan Zandberg, MD

Role: PRINCIPAL_INVESTIGATOR

UPMC Hillman Cancer Center

Locations

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UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Jennifer Ruth, RN, BSN

Role: CONTACT

Phone: 412-623-8963

Email: [email protected]

Rosemarie Angelo, RN, BSN

Role: CONTACT

Phone: 412-623-7039

Email: [email protected]

Facility Contacts

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Jennifer Ruth, RN, BSN

Role: primary

Rosemarie Angelo, RN, BSN

Role: backup

Other Identifiers

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CA224-056

Identifier Type: OTHER

Identifier Source: secondary_id

HCC 18-139

Identifier Type: -

Identifier Source: org_study_id