A Biomarker-driven, Open Label, Single Arm, Multicentre Phase II Study of Abemaciclib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Who Failed to Platinum-based Therapy

A Biomarker-driven, Open Label, Single Arm, Multicentre Phase II Study of Abemaciclib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Who Failed to Platinum-based Therapy

Open, multicenter, single arm, phase II, biomarker driven umbrella trial for head and neck squamous cell carcinoma (FGFR inhibitor, CDK4/6 inhibitor, pan HER inhibitor, PI3K inhibitor, PD1/PD-L1 inhibitor)

This study will be conducted as a treatment arm 4 of the umbrella clinical trial.(NCT03292250)

During or after palliative 1st line platinum based chemotherapy, we will perform prescreening NGS based molecular characterization. The molecular characterization will be done by following three methods.

• NGS : Agilent SureSelect Target Enrichment (245 genes)
• Nanostring nCounter including immune signature
• IHC : PD-L1

The present trial will investigate the efficacy and safety of abemaciclib in patients with recurrent or metastatic HPV (-) HNSCC with genetic alterations of cell cycle pathway who failed to platinum-based therapy. We will also evaluate feasibility and the effect on decision making of next generation sequencing of HNSCC.

Inclusion Criteria:

• (1) Histologically or cytologically confirmed recurrent or metastatic HNSCC, except nasopharyngeal carcinoma (2) Age ≥20 (3) ECOG performance status of 0-1 (4) Ineligibility for local therapy (surgery or radiotherapy) (5) Prior palliative chemotherapy including platinum-based chemotherapy. When recurred within 6 months of definitive/neoadjuvant/adjuvant chemo- or chemoradiation, the chemotherapy is considered a line of palliative chemotherapy (6) At least one measurable lesion by RECIST ver 1.1 (7) p16 negative and intact Rb and genetic alterations in CDK4/6 pathway (8) Adequate organ function for all of the following criteria, as defined below.
• Absolute neutrophil count (ANC) ≥1500 cells/mm3
• Platelets ≥100,000 cells/mm3
• Hemoglobin ≥ 8 g/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.)
• Serum creatinine ≤1.5 x institution upper limit of normal
• Total Bilirubin ≤1.5 x upper limit of normal (ULN) (Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.)
• AST (SGOT) ≤3.0 x ULN
• ALT (SGPT) ≤3.0 x ULN (9) If a female of childbearing potential, must have a negative serum pregnancy test within 7 days of the first dose of abemaciclib and agree to use a medically approved contraceptive method during the treatment period and for 3 months following the last dose of abemaciclib.

If a male, must agree to use a reliable method of birth control and to not donate sperm during the study and for at least 3 months following the last dose of abemaciclib. Contraceptive methods may include an intrauterine device [IUD] or barrier method. If condoms are used as a barrier method, a spermicidal agent should be added as a double barrier protection.

(10) Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to screening. A washout period of at least 21 days is required between last chemotherapy dose and screening (provided the patient did not receive radiotherapy).

(11) 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.

(12) The patient has provided signed informed consent and has a compliance to follow the study protocol.

(13) The patient is able to swallow oral medications.

Exclusion Criteria:

• (1) Prior treatment with CDK4/6 pathway inhibitors (2) Nasopharyngeal carcinoma (3) The patient has serious 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).

  (4) Pregnant woman, Breast-feeding woman (5) Recent significant bleeding history within 6 major vessel invasion of tumor (6) Other severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial (infection/inflammation, intestinal obstruction, social/psychological complications).

  (7) Patient who have an active systemic fungal and/or known viral infection (for example, human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C antibodies) (8) The patient has a 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.