Phase 1/2 Study of PX-866 and Cetuximab

Inclusion Criteria:

- At least 18 years at time of consent

- Use of a medically accepted form of contraception from the time of consent to
completion of all follow-up study visits

- If female of child-bearing potential, negative pregnancy test

- Signed an informed consent

- Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST)

- Documentation available for last prior systemic treatment including dates of
treatment, best response to treatment, duration of best response, and reason for
discontinuation of treatment

- Eastern Cooperative Oncology Group (ECOG) 0 or 1

- Group 1: Patients with incurable metastatic CRC with a history of progression or
recurrence following prior irinotecan and oxaliplatin containing regimens. Patients
who have a history of intolerance of irinotecan based therapy or ineligibility to
receive irinotecan are also eligible as long as they have received a prior
oxaliplatin containing regimen.

- Group 2: Patients with incurable SCCHN with a history of progression or recurrence
following at least one prior platinum based chemotherapy or chemotherapy/radiation
containing regimen. Patients who have a history of intolerance of platinum based
therapy or history of ineligibility to receive a platinum based regimen are also
eligible. SCCHN patients who received cetuximab as a radiosensitizer for locally
advanced disease and completed treatment at least 6 months prior to start of study
drug treatment are eligible

- In the opinion of the clinical investigator, life expectancy of greater than 3 months

- Adequate hematologic function

- Adequate hepatic function

- Creatinine level ≤1.5 x ULN

- Serum magnesium ≥ LLN.

Exclusion Criteria:

- Has medical, social, or psychosocial factors that, in the opinion of the
investigator, could impact safety or compliance with study procedures

- Is breastfeeding

- Treatment with any systemic chemotherapy, epidermal growth factor receptor (EGFR)
inhibitor, radiation or experimental agent within 4 weeks of study drug dosing

- Received prior cetuximab, except as defined in inclusion criteria

- Previous treatment with a phosphatidylinositol 3-kinase (PI-3K) inhibitor

- Known human immunodeficiency virus (HIV)

- Poorly controlled diabetes mellitus (IFCC-HbA1C ≥ 53 mmol/mol or DCCT -HbA1C ≥ 7%)

- Kras mutation in codon 12 or 13 (CRC patients only)

- Known or suspected clinically active brain metastases. Previously treated and stable
brain metastases are allowable. Stable brain metastases are defined as no change on
CT scan or MRI for minimum of two months AND no change in steroid dose for a minimum
of four weeks, unless change due to intercurrent infection or other acute event)

- Any other significant medical or psychiatric condition that in the opinion of the
investigator renders the patient inadequate for participation

- History of severe hypersensitivity to cetuximab