Study of Xevinapant With Radiation and Chemotherapy for Patients With Head and Neck Cancer

Inclusion Criteria

• •1. Pathologically proven diagnosis of squamous cell carcinoma of the head and neck (HNSCC) of the oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, or sinuses.
• •* Patients with oropharynx cancer need p16 determination by immunohistochemistry (where positive is defined as greater than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells).
• •* Oral cavity, larynx, hypopharynx, or p16-negative oropharynx cancer must be stages T1-2N1-3 or T3-4N0-3 (AJCC 8th edition). Sinus primary must be T4bN0-3 not amenable to surgical resection.
• •* P16-positive oropharynx cancer patients, stages T1-2N1-3 or T3-4N0-3 (AJCC 8th edition staging).
• •2. The patient has unresected, measurable disease as defined by the presence of at least one measurable lesion per RECIST 1.1.
• •3. Age \>= 18 years of age
• •4. Patients must have a contraindication to cisplatin
• •5. Performance Status of 0-2
• •6. Adequate hematologic function
• •* White Blood Cell Count (WBC) \>= 2000 cells/mm3
• •* Absolute neutrophil count (ANC) \>= 1,500 cells/mm3
• •* Platelets \>= 100,000 cells/mm3
• •* Hemoglobin \>= 9.0 g/dL
• •7. Adequate renal function was defined as follows: Creatinine clearance (CrCl) \> 30 mL/min
• •8. Adequate hepatic function
• •* Total bilirubin \<= 1.5 x upper limit of normal (ULN) (except patients with Gilbert Syndrome who can have total bilirubin \< 3.0 mg/dL)
• •* aspartate aminotransferase (AST) and alanine transaminase (ALT) \<= 2.5 x upper limit of normal (ULN)
• •9. For women of childbearing potential (e.g. uterus present and menstruating), a negative serum pregnancy test within 14 days prior to registration.
• •10. Willingness to agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from time of joining the study until 6 months after completing chemotherapy treatment or 3 months after last dose of xevinapant, whichever is the latest.
• •12. Ability to understand and the willingness to sign a written informed consent document.
• •13. Availability of tumor tissue for research analysis. Patients who do not have adequate tissue available will need to undergo a new biopsy prior to enrollment on study.