Inclusion Criteria:

1. Age more than or equal to 18 years
2. Histologically or cytologically confirmed squamous cell carcinoma of head and neck that is recurrent and/or metastatic and judged incurable by surgery and/or radiation therapy. Subjects with locally advanced non-metastatic and/or non-recurrent disease could be enrolled if the tumor is unresectable and has been demonstrated to be refractory to at least one regimen of chemotherapy besides being judged incurable by radiation therapy.
3. Measurable disease, defined as at least one unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥10 mm by spiral computerized tomography (CT) scan or magnetic resonance imaging (MRI)
4. Tumor that is accessible to biopsy
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
6. Life expectancy of at least three months
7. Hemoglobin ≥ 8.0 gm/dL
8. Absolute neutrophil count (ANC) ≥ 1000/mm3
9. Platelet count ≥ 50,000/mm3
10. Total bilirubin ≤1.5X institutional upper limit of normal (ULN)
11. Serum AST ≤ 3X institutional ULN
12. Serum ALT ≤ 3X institutional ULN
13. Serum creatinine ≤1.5X institutional ULN
14. Ability to understand and the willingness to sign a written informed consent document (ICD)

Exclusion Criteria:

1. Nasopharyngeal carcinoma
2. Prior treatment with P276-00 or other Cyclin dependent kinase (CDK) targeting agents
3. History of allergic reactions attributed to compounds of similar chemical composition to P276-00
4. Subjects who have received radiotherapy, chemotherapy or biologic/targeted anticancer agents within 4 weeks prior to Day 1 of study drug administration (6 weeks for nitrosoureas or mitomycin C) or have not recovered from adverse effects of any prior radiotherapy, chemotherapy or biologic/targeted agents
5. More than one chemotherapy regimen for the recurrent or metastatic disease
6. Subjects who had received any other investigational drug within 1 month or within five half-lives of the other investigational agent, whichever is longer prior to Day 1 of study drug administration
7. Subjects with QTc > 450 msec on 12 lead standard electrocardiogram (ECG)
8. History of unstable angina or myocardial infarction or stroke within previous 6 months
9. Subjects with uncontrolled inter-current illness including, but not limited to active infection, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
10. Subjects known to be suffering from infection with HIV, Tuberculosis, Hepatitis C or Hepatitis B
11. Known brain metastasis
12. History of prior malignancy except for curatively treated basal cell or squamous cell carcinoma of skin, in situ cervical cancer, in situ breast cancer, in situ prostate cancer or any other cancer for which the subject has been disease-free for at least 3 years
13. Women who are pregnant or lactating
14. Women of childbearing potential [defined as sexually mature women who have not undergone hysterectomy or who have not been naturally postmenopausal for at least 24 consecutive months (i.e. who have had menses any time in the preceding 24 consecutive months)] and men, not agreeing to use adequate contraception (e.g., hormonal or barrier method of birth control or abstinence) prior to study entry (after signing the ICD), during the period of study participation and for at least 4 weeks after withdrawal from the study, unless they are surgically sterilized
15. Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at an unacceptable risk or deems the subject not suitable for participation in the study