Abemaciclib + Nivolumab in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma That Progressed or Recurred Within Six Months After Platinum-based Chemotherapy

Inclusion Criteria:

- Incurable RM-HNSCC, defined as disease not amenable to cure by surgery and/or
radiation therapy (or patient declines or is ineligible for surgery and/or radiation
therapy).

- Disease Evaluation:

- Phase I: evaluable or measurable disease.

- Phase II: measurable disease, defined as lesions that can be accurately measured
in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT
scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm by clinical exam.

- Prior Treatment:

- Phase I: any number of lines of prior therapy for RM-HNSCC.

- Phase I: prior therapy with inhibitors of CDK4/6 or PD-L1/PD-1 is acceptable.

- Phase II: RM-HNSCC that progressed or recurred within six months of
platinum-based therapy (given for curable or incurable disease).

- Phase II: prior therapy with inhibitors of CDK4/6 or PD-L1/PD-1 is not
acceptable.

- 18 years of age or older

- Performance status 0-1 (ECOG)

- Adequate blood and organ function as defined:

- Absolute neutrophil count ≥ 1,500/mcL

- Platelets ≥ 100,000/mcL

- Hemoglobin ≥ 9.0 g/dL

- Total bilirubin ≤ 1.5 mg/dL

- AST(SGOT) ≤ 5 x IULN and ALT(SGPT) ≤ 5 x IULN

- Creatinine ≤ 2 x ULN OR creatinine clearance ≥ 40 mL/min/1.73 m2

- INR ≤ 1.5 x ULN and PTT ≤ 1.5 x ULN (Patients are allowed to be on
anticoagulation)

- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) beginning 14 days prior to
first dose of abemaciclib, through the dosing period, and for at least 28 days after.

- Signed IRB approved written informed consent document.

Exclusion Criteria:

- Phase II: prior inhibitors of CDK4/6 or PD-L1/PD-1 for treatment of incurable HNSCC.

- Radiation, chemotherapy, targeted or investigational therapy within 14 days of
treatment start.

- History of other malignancy ≤ 1 year prior to consent with the exception of completely
resected skin carcinoma or other cancers with a low risk of recurrence.

- Ongoing toxicity attributed to prior anti-cancer therapy that is > grade 1, except
alopecia, anemia, fatigue or rash.

- Active central nervous system metastases: defined as currently receiving radiation
therapy to metastatic CNS disease. Once radiation therapy is completed, patients with
CNS disease are eligible if they meet all other criteria for enrollment.

- History of severe allergic reactions attributed to agents used in the study.

- Serious uncontrolled inter-current illness within the 3 months prior to study entry or
psychiatric illness/social situations that would limit compliance with study
requirements.

- Pregnant and/or breastfeeding. Patient must have a negative serum pregnancy test
within 7 days of first dose of treatment.

- Active serious autoimmune disease requiring systemic immunosuppression (biologics,
prednisone equivalent dose > 20 mg/day).

- Current use of strong CYP3A inhibitors or inducers.