Immunotherapy has been recently approved for patients with metastatic or recurrent squamous
cell carcinoma of the head and neck. However, only a small percentage of patients experience
long-term control, necessitating new therapeutic strategies. Recently, it was shown
preclinically and in breast tumors that abemaciclib stimulates production of type III
interferons and hence enhances tumor antigen presentation. Abemaciclib also suppressed the
proliferation of regulatory T cells. These events promote cytotoxic T-cell-mediated clearance
of tumor cells, which is further enhanced by the addition of immune checkpoint blockade.
Based on these data, a phase II trial in patients with metastatic or recurrent head and neck
cancer who are eligible for immunotherapy is proposed to investigate the combination of
abemaciclib with pembrolizumab. Tumor & blood analysis for interferon gamma signature will be
explored as possible biomarkers.
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
