Oral Rigosertib for Squamous Cell Carcinoma

Inclusion Criteria:

1. Histologically confirmed SCC; only patients with HNSCC, non-small cell lung SCC, skin SCC, cervical SCC, penile SCC, anal SCC, or esophageal SCC;
2. For patients with HNSCC only, HPV status must be assessed by in situ hybridization (ISH) and/or p16 immunohistochemistry (IHC) according to local standards;
3. For patients with HNSCC only, HPV status must be assessed by in situ hybridization (ISH) and/or p16 immunohistochemistry (IHC) according to local standards. For all other patients with SCC originating in tissues other than the head and neck, attempts should be made to obtain HPV status;
4. Incurable, non-resectable, locally-advanced/relapsed and/or distant metastatic disease after no more than 3 prior treatment regimens, one of which must be platinum-based chemotherapy;
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤2;
6. Life expectancy of at least 3 months;
7. Measurable disease according to RECIST version 1.1;
8. Ability to swallow entire capsules;
9. Adequate hematologic function;
10. Adequate hepatic function;
11. Adequate renal function;
12. Adequate contraceptive regimens for female and male patients;
13. Female patients with reproductive potential must have a negative urine or serum pregnancy test;
14. Ability to understand the nature of the study and any hazards of study participation, to communicate satisfactorily with the Investigator, and to follow the requirements of the entire protocol;
15. Willingness to adhere to the prohibitions and restrictions specified in this protocol;
16. The patient must sign an informed consent form (ICF).

Exclusion Criteria:

1. Chemotherapy or any potentially myelosuppressive treatment within 3 weeks prior to enrollment (6 weeks are required for nitrosoureas or mitomycin C);
2. Radiotherapy to \>25% of the hematopoietic active bone marrow within 4 weeks prior to enrollment;
3. Systemic administration of corticosteroids within the past 4 weeks prior to enrollment;
4. Prior therapy with a phosphatidylinositol 3-kinase (PI3K), Akt or mammalian target of rapamycin (mTOR) inhibitor;
5. Any other investigational agent or chemotherapy, radiotherapy, or immunotherapy within 4 weeks of enrollment;
6. Major surgery within 3 weeks of enrollment or major surgery without full recovery;
7. Residual clinical signs and symptoms which have not recovered to Common Terminology Criteria for Adverse Events (CTCAE) version 4 Grade 1 severity level or below before enrollment, except for alopecia, stable residual neuropathy, and residual hand/foot syndrome;
8. Known brain metastases, except for those that have been removed or irradiated and have no current clinical impact at the time of enrollment; a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the brain should be obtained in patients with symptoms suggestive of brain metastases;
9. Ascites requiring active medical management, including paracentesis;
10. Serum sodium less than 130 mEq/L or conditions that may predispose patients to hyponatremia (eg, previous syndrome of inappropriate antidiuretic hormone hypersecretion \[syndrome of inappropriate antidiuretic hormone secretion (SIADH)\], chronic diuretic use, etc.);
11. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, bleeding, symptomatic congestive heart failure, unstable angina pectoris, and cardiac arrhythmia;
12. Uncontrolled hypertension, defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥110 mmHg;
13. New onset of seizures within 3 months prior to enrollment, or poorly controlled seizures;
14. Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements;
15. History of allergic reactions attributed to compounds of similar chemical or biologic composition to rigosertib;
16. Female patients who are pregnant or lactating.