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.