In phase I of the trial, the investigators aim to explore the safety and feasibility of
abemaciclib in combination with nivolumab in patients with recurrent/metatstatic head and
neck squamous cell carcinoma (RM-HNSCC). A dose de-escalation study design will be used to
determine the recommended phase II dose (RP2D) of abemaciclib given with the standard dose of
In phase II of the trial, the investigators aim to determine if abemaciclib and nivolumab
will improve the one year survival from 36% (historical comparison with nivolumab) to 60%
(abemaciclib + nivolumab) in patients with RM-HNSCC that had progressed or recurred within
six months after platinum-based chemotherapy. Patients will be treated with abemaciclib at
the recommended phase 2 dose (RP2D) in combination with standard doses of nivolumab. If this
aim is met, genome sequencing, bulk and single cell RNAseq, and selected protein expression
and deep cellular phenotyping will be performed on tumor tissue and blood obtained before and
during treatment with abemaciclib and nivolumab. These biomarker data will be correlated with
survival and tumor response to abemaciclib and nivolumab.
- 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
- 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
- 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 ≥ 8.0 g/dL
- Total bilirubin ≤ 1.5 x ULN mg/dL
- AST(SGOT) ≤ 3 x IULN and ALT(SGPT) ≤ 3 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
- Able to swallow oral medication
- 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.
- Phase II: prior inhibitors of CDK4/6 or PD-L1/PD-1 for treatment of incurable HNSCC.
- Radiation within 14 days of treatment start (patients who received radiotherapy must
have completed and fully recovered from the acute side effects of radiotherapy),
chemotherapy, targeted or investigational therapy within 21 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 or peripheral neuropathy
- 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
- Serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of
the investigator, would preclude participation in this study (i.e., interstitial lung
disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment
[e.g. estimated creatinine clearance <30ml/min], 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
- Active systemic 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 with known active hepatitis B or C
[for example, hepatitis B surface antigen positive]. Screening is not required for
- 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.
- 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.