Abemaciclib and Pembrolizumab in Metastatic or Recurrent Head and Neck Cancer
Condition: Head and Neck Cancer
MeSH terms: Head and Neck Neoplasms
Intervention: Cohort 1 Not Previously Treated; Cohort 2 Treated Previously
Intervention description: Abemaciclib 150mg by mouth twice daily Pembrolizumab 200mg IV every 3 weeks; Abemaciclib 150mg by mouth twice daily Pembrolizumab 200mg IV every 3 weeks
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: immunotherapy; abemaciclib; pembrolizumab; Cyclin-Dependent Kinase (CDK): CDK4; Cyclin-Dependent Kinase (CDK): CDK6

Summary:

      To assess the objective response rate of tumor lesions to abemaciclib in combination with
      pembrolizumab in patients with metastatic or recurrent squamous cell carcinoma of head and
      neck.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed (core biopsy proven) metastatic or recurrent squamous cell
             carcinoma of head and neck

          -  Adequate pulmonary and cardiac function

          -  Available archived tissue of primary tumor or resected tumor specimen with adequate
             samples

          -  Prior treatment with immune checkpoint inhibitor is not allowed in cohort 1 patients.
             Patients in cohort 2 should have failed or progressed on prior immune checkpoint
             inhibitor

          -  Eastern Cooperative Oncology Group Performance Status(ECOG PS) = 0 or 1

          -  Patients who received chemotherapy must have recovered (Common Terminology Criteria
             for Adverse [CTCAE] Grade <= 1) from the acute effects of chemotherapy except for
             residual alopecia or Grade 2 peripheral neuropathy prior to randomization. A washout
             period of at lease 21 days is required between last chemotherapy dose and
             randomization (provided the patient did not receive radiotherapy)

          -  Patients who received adjuvant radiotherapy must have completed and fully recovered
             from the acute effects of radiotherapy. A washout period of at least 14 days is
             required between end of radiotherapy and randomization

          -  The patient is able to swallow oral medications

          -  Adequate hematologic and end-organ function

          -  Absolute Neutrophil Count (ANC) >= 1500/mm3

          -  Platelet count ≥ 100,000/mm3

          -  Hemoglobin (Hb) ≥ 8g/dl (Patients may receive erythrocyte transfusions to achieve this
             hemoglobin level at the discretion of the investigator. Initial treatment must not
             begin earlier than the day after the erythrocyte transfusion)

          -  Creatinine (Cr) ≤ 1.5 x Upper Limit of Normal (ULN) or Creatinine Clearance (CrCl) ≥
             60 ml/min

          -  Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert syndrome, who can have total
             Bilirubin < 2.0 x ULN and direct bilirubin within normal limits are permitted.)

          -  Aspartate Aminotransferase (AST) and Alanine aminotransferase (ALT) and alkaline
             phosphatase ≤ ULN

          -  Agreement to remain abstinent or use appropriate contraception, among women of
             childbearing potential

          -  Willingness and ability to consent for self to participate in study

          -  Willingness and ability to comply with scheduled visits, treatment plan, laboratory
             tests, and other study procedures

        Exclusion Criteria:

          -  Autoimmune disease (Note: Vitiligo, type 1 diabetes mellitus, residual hypothyroidism
             due to autoimmune thyroiditis only requiring hormone replacement, and conditions not
             expected to recur in the absence of an external trigger are permitted.)

          -  Condition requiring systemic treatment with either corticosteroids (>10 mg daily
             prednisone equivalent) or other immunosuppressive medications within 14 days prior to
             study treatment (Note: Inhaled and topical steroids, and adrenal replacement steroid
             doses > 10 mg daily prednisone equivalent, are permitted in the absence of active
             autoimmune disease.)

          -  Preexisting medical condition(s) that would preclude participation in this study (for
             example, interstitial lung disease, severe dyspnea at rest or requiring oxygen
             therapy, history of major surgical resection involving the stomach or small bowel, or
             preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition
             resulting in baseline Grade 2 or higher diarrhea).

          -  Immunosuppression, of any kind

          -  Prior treatment with Cyclin-Dependent Kinase(CDK) 4/6 Inhibitor

          -  Major surgical procedure or significant traumatic injury within 4 weeks prior to study
             treatment, and must have fully recovered from any such procedure

          -  Personal history of any of the following conditions: syncope of cardiovascular
             etiology, ventricular arrhythmia of pathological origin (including, but not limited
             to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest

          -  Angina, myocardial infarction (MI), symptomatic congestive heart failure,
             cerebrovascular accident, transient ischemic attack TIA), arterial embolism, pulmonary
             embolism, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery
             bypass grafting (CABG) within 6 months prior to study treatment

          -  Known active viral or non-viral hepatitis or cirrhosis

          -  Any active infection requiring systemic treatment, positive tests for Hepatitis B
             surface antigen or Hepatitis C ribonucleic acid (RNA).

          -  History of gastrointestinal perforation or fistula in the 6 months prior to study
             treatment, unless underlying risk has been resolved (e.g., through surgical resection
             or repair)

          -  Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
             related illness

          -  Pregnancy or breastfeeding - Female patients must be surgically sterile (i.e., ≥6
             weeks following surgical bilateral oophorectomy with or without hysterectomy or tubal
             ligation) or be postmenopausal, or must agree to use effective contraception during
             the study and for 4 months following last dose of treatment. All female patients of
             reproductive potential must have a negative pregnancy test (serum or urine) within 7
             days prior to study treatment. Male patients must be surgically sterile or must agree
             to use effective contraception during the study and for 4 months following last dose
             of treatment.

          -  Other severe acute or chronic medical or psychiatric condition or laboratory
             abnormality that may increase the risk associated with study participation or may
             interfere with the interpretation of study results and, in the judgment of the
             Investigator, would make the patient inappropriate for this study