Abemaciclib and Nivolumab in Treating Patients with Recurrent or Metastatic Head and Neck Squamous Cell Cancer that Progressed or Recurred after Platinum-Based Chemotherapy

Status: Active


This phase I / II trial studies the side effects and best dose of abemaciclib and how well it works when given together with nivolumab in treating patients with head and neck squamous cell cancer that has come back or that has spread to other parts in the body and for which no treatment is currently available after platinum-based chemotherapy. Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving abemaciclib and nivolumab may work better in treating patients with recurrent or metastatic head and neck cancer.

Eligibility Criteria

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: * Evaluable or measurable disease (Phase I) * 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 (Phase II)
  • Prior Treatment: * 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 I) * 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 (Phase II)
  • Performance status 0-1 (Eastern Cooperative Oncology Group [ECOG])
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 9.0 g/dL
  • Total bilirubin =< 1.5 mg/dL
  • Aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 5 x institutional upper limit of normal (IULN) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 x IULN
  • Creatinine =< 2 x ULN OR creatinine clearance >= 40 mL/min/1.73 m^2
  • International normalized ratio (INR) =< 1.5 x ULN and partial thromboplastin time (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 Institutional Review Board (IRB) approved written informed consent document
  • History of severe allergic reactions attributed to agents used in the study

Exclusion Criteria

  • Prior inhibitors of CDK4/6 or PD-L1/PD-1 for treatment of incurable HNSCC (Phase II)
  • Radiation, chemotherapy, targeted or investigational therapy within 14 days of treatment star
  • 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 central nervous system (CNS) disease. Once radiation therapy is completed, patients with CNS disease are eligible if they meet all other criteria for enrollment
  • 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.

Locations & Contacts


Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Contact: Douglas Ray Adkins
Phone: 314-747-8475
Email: dadkins@wustl.edu

Trial Objectives and Outline


I. Determine the recommended phase II dose (RP2D) of abemaciclib combined with a fixed dose of nivolumab in patients with recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC). (Phase I)

II. Determine the overall survival (OS) of patients with RM-HNSCC that progressed or recurred within six months of platinum-based therapy who are treated with abemaciclib and nivolumab. (Phase II)


I. Determine the best tumor response rate for patients with RM-HNSCC who are treated with abemaciclib and nivolumab. (Phase II)

II. Determine the duration of tumor response for patients with RMHNSCC who are treated with abemaciclib and nivolumab. (Phase II)

III. Determine the progression-free survival (PFS) for patients with RMHNSCC who are treated with abemaciclib and nivolumab. (Phase II)

IV. Determine the adverse events (AEs) associated with the combination of abemaciclib and nivolumab. (Phase II)


I. Collect and store pre-treatment and on-treatment tissue and blood specimens from patients for correlative studies, including studies of tumor heterogeneity that may define the malignant, stromal, and immune response with treatment. (Phase II)

II. Monitor quality of life (QOL) as documented by QOL measurements using the Functional Assessment of Cancer Therapy Head and Neck (FACT H&N) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 assessment tools. (Phase II)


Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28 and nivolumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 28 days and then periodically.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type


Lead Organization

Lead Organization
Siteman Cancer Center at Washington University

Principal Investigator
Douglas Ray Adkins

Trial IDs

Primary ID 201810019
Secondary IDs NCI-2018-02242
Clinicaltrials.gov ID NCT03655444