Immune Modulation by Abemaciclib in HNSCC. (AIM Trial)

Eligibility Criteria

• 1. Cytologic or histologic diagnosis of squamous cell carcinoma of the oral cavity, p16-negative oropharynx, hypopharynx, or larynx.
• 2. Tumors must be HPV-negative. For eligibility, tumors of the oral cavity, hypopharynx, or larynx will be considered HPV-negative without specialized testing. Tumors of the oropharynx must be HPV-negative as determined by p16 immunohistochemistry and/or HPV-DNA per local standard.
• 3. Clinical stage I-IVa based upon the American Joint Committee on Cancer (AJCC) staging manual, 8th edition.
• 4. Appropriate and planned for oncologic resection of the primary tumor and/or neck dissection.
• 5. Clinically or radiologically measurable disease; the primary tumor and/or cervical nodes may be measurable according to RECIST 1.1 (tumor diameter ≥ 1 cm; short-axis lymph node diameter ≥ 1.5 cm) OR by caliper/ruler measurement (tumor diameter ≥ 1 cm).
• 6. No prior treatment for the index (study-qualifying) HNSCC.
• 7. Patients with two simultaneous primary tumors or bilateral tumors are included.
• 8. The index HNSCC may be a second primary HNSCC, provided the following criteria are met:
• 9. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. (See Appendix 1.)
• 10. Adequate hematologic function, as defined by:
• 11. Adequate liver function, as defined by:
• 12. Adequate renal function, as defined by creatinine ≤ 1.5 x ULN.
• 13. Able to swallow oral medications.
• 14. Have signed written informed consent.
• 15. Consent to biomarker collection requirements, including mandatory baseline and intra-operative research biopsies of the index tumor.
• 1. Prior treatment with any cyclin-dependent kinase (CDK) 4/6 inhibitor or anti-programmed death (PD)-1/L1 inhibitor is not allowed.
• 2. Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned protocol treatment. The following are exceptions to this criterion unless otherwise indicated:
• 1. Intranasal, inhaled, or topical steroids, or local steroid injections (eg, intra articular injection)
• 2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• 3. Steroids as premedication for hypersensitivity reactions (eg, CT premedication) and/or as anti-emetics
• 3. Active or previously documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis, Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, sarcoidosis syndrome, Wegener syndrome \[granulomatosis with polyangiitis\], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.). The following are exceptions to this criterion:
• 1. Patients with vitiligo or alopecia
• 2. Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement. Subclinical hypothyroidism (eg. Elevated thyroid-stimulating hormone (TSH), low or normal free T4, and asymptomatic) observed on screening labs is not an exclusion.
• 3. Any chronic skin condition that does not require systemic therapy
• 4. Patients without active disease in the last 5 years may be included but only after consultation with the study PI
• 5. Patients with celiac disease controlled by diet alone
• 4. Patient has a personal history of any of the following cardiac or pulmonary abnormalities:
• 1. Syncope of cardiovascular etiology
• 2. Ventricular arrhythmia of pathologic origin (including, but limited to, ventricular tachycardia and ventricular fibrillation)
• 3. Sudden cardiac arrest
• 4. Documented history of New York Heart Association functional classification III-IV congestive heart failure
• 5. Myocardial infarction ≤ 6 months prior to enrollment
• 6. Current unstable angina pectoris
• 7. Interstitial lung disease
• 8. Severe dyspnea at rest or requiring oxygen therapy
• 5. Patient with impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral abemaciclib (e.g. history of major surgical resection involving the stomach or small bowel, malabsorption syndrome, preexisting Crohn's disease or ulcerative colitis, preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
• 6. Patients who require the chronic administration of drugs that are strong and moderate inducers of Cytochrome P450, family 3, subfamily A, (CYP3A) and/or strong inhibitors of CYP3A, and no acceptable substitute can be identified, are not eligible for study (See Appendix 2). Such drugs should be discontinued at least 7 days before the start of study treatment.
• 7. The patient has active bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or known active hepatitis B or C \[e.g. hepatitis B surface antigen positive or hepatitis C antibody positive with detectable viral load\]). Screening for HIV or hepatitis is not required for enrollment.
• 8. Patient with any other condition that would, in the Investigator's judgment, preclude patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g. social/psychological complications.
• 9. Pregnant or nursing (lactating) women.
• 10. Patient who does not apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment:
• 1. Sexually active males should use a condom during intercourse while taking abemaciclib and for 4 weeks after the final dose of abemaciclib.
• 2. Males who are sexually active with a woman of child-bearing potential should apply highly effective contraception during the study as defined below, in order not to father a child in this period.
• 3. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through at least 3 weeks after the final dose of abemaciclib. Highly effective contraception is defined as:
• 1. Placement of an intrauterine device (IUD) or intrauterine system (IUS) 2. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
• 11. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.