Inclusion Criteria:

1. Able to provide signed and dated informed consent document prior to study-specific screening procedures.
2. Histologically or cytologically confirmed locally advanced, recurrent or metastatic SCCHN.
3. Measurable disease per RECIST.
4. ≥ 18 years old.
5. Karnofsky performance status (KPS) ≥ 70%.
6. Male or female patients of child-producing potential must agree to use contraception or avoidance of pregnancy measures during the study and for 30 days after the last infusion of ARQ 501.
7. Hemoglobin (Hgb) ≥ 10 g/dL.
8. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (≥ 1,500/mm³).
9. Platelet count ≥ 100 x 10^9/L ( ≥ 100,000/mm³).
10. Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN) or less than or equal to 3.0 x ULN with metastatic liver disease.
11. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x ULN or less than or equal to 5.0 x ULN with metastatic liver disease.
12. Creatinine less than or equal to 1.5 x ULN.

Exclusion Criteria:

1. Primary tumor of nasopharyngeal origin.
2. Eligible for curative surgery or radiotherapy.
3. Received three or more systemic anticancer regimens.
4. Have active, uncontrolled systemic infection considered opportunistic, life threatening or clinically significant at the time of treatment.
5. Have received anticancer chemotherapy, immunotherapy, radiotherapy, or investigational agents within three weeks of first infusion.
6. Surgery within two weeks of first infusion.
7. Have symptomatic or untreated central nervous system (CNS) involvement.
8. Are pregnant or lactating.
9. Previous exposure to ARQ 501.