Nivolumab Alone or in Combination with Relatlimab or Ipilimumab for the Treatment of Resectable Stage III-IVA Head and Neck Cancer
- Histologically or cytologically confirmed squamous cell carcinoma, previously untreated stage III, or IVA head and neck carcinoma (HNC) by American Joint Committee on Cancer (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 human papillomavirus (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 magnetic resonance imaging (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
- Left ventricular ejection fraction (LVEF) assessment with documented LVEF >= 50% by either transthoracic echocardiography (TTE) or multigated acquisition scan (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
- Eastern Cooperative Oncology Group (ECOG) performance status 0–1
- Have signed written informed consent
- Prior radiation, chemotherapy, oncology vaccine or immunotherapy
- Prior severe infusion reaction to a monoclonal antibody
- Troponin T (TnT) or I (TnI) > 2 x institutional upper limit of normal (ULN). Subjects with TnT or TnI levels between > 1 to 2 x ULN will be permitted if repeat levels within 24 hours are =< 1 x ULN. If TnT or TnI levels are > 1 to 2 x ULN within 24 hours, the subject may undergo a cardiac evaluation and be considered for treatment, following a discussion with the Bristol-Myers Squibb (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 examination under anesthesia (EUA), the subject will be excluded from study participation
I. To assess the safety of relatlimab given in combination with nivolumab compared to nivolumab and ipilimumab or nivolumab alone in subjects with locally advanced, resectable head and neck squamous cell carcinoma (HNSCC) prior to surgery.
I. To assess the radiographic and/or pathologic response to of relatlimab given in combination with nivolumab compared to nivolumab and ipilimumab or nivolumab alone in subjects with locally advanced, resectable HNSCC prior to surgery.
II. To assess the changes in immune biomarkers and the tumor immune microenvironment and the predictive value of these biomarkers in patients with locally advanced, resectable HNSCC treated with relatlimab given in combination with nivolumab compared to nivolumab and ipilimumab or nivolumab alone prior to surgery.
IIa. To assess the pharmacodynamic effect on tumor infiltrating lymphocyte (TIL) subsets and peripheral blood lymphocytes (PBL) from HNSCC subjects treated with this combination.
IIb. To explore potential associations between immune biomarker measures in effector (CD8 positive [+] and CD4+) and regulatory T cells (Treg) and anti-tumor activity as measured by change in tumor volume on computed tomography (CT) scan.
IIc. To explore mutational burden and single cell ribonucleic acid sequencing (RNAseq) pathways.
OUTLINE: Patients are randomized to 1 of 3 groups.
GROUP I: Patients receive nivolumab intravenously (IV) over 60 minutes and relatlimab IV over 60 minutes on day 1. Patients may also receive nivolumab IV over 60 minutes and relatlimab IV over 60 minutes on day 28 per physician discretion if surgery is postponed. Within 28-31 days after therapy, patients undergo surgical resection.
GROUP II: Patients receive nivolumab IV over 60 minutes on days 1 and 14 and ipilimumab IV over 60 minutes on day 1. Patients may also receive nivolumab IV over 60 minutes on day 28 per physician discretion if surgery is postponed. Within 28-31 days after therapy, patients undergo surgical resection.
GROUP III: Patients receive nivolumab IV over 60 minutes on day 1. Patients may also receive nivolumab IV over 60 minutes on day 28 per physician discretion if surgery is postponed. Within 28-31 days after therapy, patients undergo surgical resection.
After completion of study treatment, patients are followed up at 1, 3, and 6 months after surgery.
Trial Phase Phase II
Trial Type Treatment
University of Pittsburgh Cancer Institute (UPCI)
Robert Louis Ferris
- Primary ID HCC 18-139
- Secondary IDs NCI-2020-02015
- Clinicaltrials.gov ID NCT04080804