Neoadjuvant Targeting of Myeloid Cell Populations in Combination With Nivolumab in Head & Neck Cancer Patients Undergoing Surgery
Neoadjuvant Targeting of Myeloid Cell Populations in Combination With Nivolumab in Head & Neck Cancer Patients Undergoing Surgery
The primary objective of this study is to assess safety and feasibility of pre-operative nivolumab in combination with BMS-986253 (anti-interleukin-8) in patients with squamous cell carcinoma of head and neck (SCCHN) who will undergo surgery.
Inclusion Criteria:
The primary site should be a head and neck squamous cell carcinoma (including, but not limited to oral cavity, oropharynx, hypopharynx, or larynx, paranasal sinuses, nasal cavity). Squamous cell carcinoma of unknown primary, diagnosed in lymph nodes in neck, can be included but should be tested for p16 and confirmed with an HPV specific assay (testing NOT required for enrollment; can be done at an interval).
Subjects must be human papillomavirus (HPV) negative (confirmed testing for oropharyngeal primary tumors - if otherwise suspected HPV positivity e.g. some oral cavity or sinonasal tumors if e.g. absence of smoking) OR (if HPV+) be high risk based on a ≥20 pack year smoking history.
HPV testing is required per clinical standards
Subjects must have been determined to be candidates for surgical resection by a multidisciplinary team including a surgeon, a medical oncologist and a radiation oncologist. Resection should typically be definitive but may also be done for symptomatic control e.g. in the setting of (suspected) metastatic disease with dominant local symptoms.
Subjects must have at least one lesion that can be (or has been) biopsied at baseline.
Patients with metastatic disease (both HPV(-) and high-risk HPV(+) (i.e. ≥20 pack years of smoking) are allowed, as long as patients have an indication for surgery for locoregional disease, and a life expectancy of ≥6 months. Metastatic disease can be addressed with additional treatments after trial treatment, e.g. focal radiation, or additional systemic therapy (e.g. chemotherapy or as indicated a targeted therapy or standard of care immunotherapy).
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
Age greater than or equal to 18 years
Life expectancy of greater than 6 months
Patients must have normal organ and marrow function
The effects of nivolumab, as well as the other agents in this study on the developing human fetus are unknown.
Patient understands the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form. Voluntary signed and dated Institutional Review Board (IRB) approved written informed consent form in accordance with regulatory and institutional guidelines must be obtained before the performance of any protocol related procedures that are not part of normal patient care. Subjects must be competent to report AEs, understand the drug dosing schedule and use of medications to control AEs
Measurable disease - either radiologically (per RECIST) or clinically measurable on exam in order to assess treatment response.
Exclusion Criteria:
Patients with brain metastases must have stable neurologic status following local therapy (surgery and/or radiation) for at least 2 weeks without the use of steroids or on stable or decreasing dose of ≤ 10mg daily prednisone (or equivalent), and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of carcinomatous meningitis are not eligible.
However, patients with metastatic disease (both HPV(-) and high-risk HPV(+) (i.e. ≥20 pack years of smoking) are allowed, as long as patients have an indication for surgery for locoregional disease, and a life expectancy for ≥6 months. Metastatic disease can be addressed with additional treatments after trial treatment, e.g. focal radiation, or additional systemic therapy (e.g. chemotherapy or as indicated a targeted therapy or standard of care immunotherapy).
Patients who have an active concurrent malignancy that is not controlled/cured and could impact life expectancy within the next 3 years. E.g. patients with localized cutaneous squamous cell carcinoma or basal cell carcinoma or treated prostate cancer with no evidence of disease progression may be allowed to enroll after review by the study team and principal investigator.
Uncontrolled inter-current illness including, but not limited to, no clinically significant active infection requiring (antimicrobial) treatment in the last week, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, myocardial infarction or new onset angina within six months of enrollment, or psychiatric illness/social situations that would limit compliance with study requirements.
Women who are pregnant or nursing
Men with female partners who are not willing to use contraception (Contraception method defined in protocol)
Active infection with hepatitis B or hepatitis C (active infection is defined by either a) abnormal liver function tests (=elevated aspartate aminotransferase/alanine aminotransferase) or b) ongoing use of an antiviral hepatitis treatment).
Patients with a condition requiring chronic systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study start. However, inhaled or topical steroids and adrenal replacement steroid doses < 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. Also, a burst of steroids (≤10 days use, e.g. a contrast premedication, or a methylprednisolone dose pack or similar) are acceptable and not excluded.
Epstein-Barr Virus (EBV) positive head and neck cancer (e.g. EBV(+) nasopharyngeal carcinoma)
Patients with HIV are excluded given the unknown risk of interaction with HAART and the unknown benefit of immunotherapy in this population.