Inclusion Criteria:

- Histological or cytological diagnosis of advanced/metastatic solid tumor for which
there is no currently clinically effective treatment.

- All tumor types for patients enrolled in Stage 1 of Arm C.

- For patients enrolled in Stage 2 of Arm C, advanced colorectal cancer (both KRAS
mutated and KRAS wild type), which has progressed on irinotecan-based regimens, and
pancreatic ductal adenocarcinoma after progression on first line treatment for
metastatic/advanced disease.

- For patients enrolled in Stage 1 of Arm D, tumors with KRAS or BRAF mutation
(archived or fresh biopsy). Patients with tumors harboring other mutations that
activate the MAPK pathway may be enrolled upon agreement with the Sponsor.

- For patients enrolled in Stage 2 of Arm D, advanced colorectal cancer KRAS mutated
(archived or fresh biopsy), which has progressed on irinotecan-based regimens.

- Patients with colorectal cancer enrolled to both Arms must:

1. have received at least 6 weeks of irinotecan-based therapy (either as single
agent or in combination with cytotoxic drugs or in combination with targeted
therapies) as the last prior treatment

2. have progressed on or within 1 month of completing this irinotecan-based regimen

- All patients must provide an archived or fresh tumor sample.

- For a subset of patients fresh tumor biopsies are mandatory:

1. All patients with CRC enrolled to Stage 2 of Arm C must provide a fresh tumor
biopsy at baseline. A subset of patients (10 or more) with at least 5 evaluable
patients with CRC KRAS wild type must also provide tumor biopsy during
treatment.

2. Paired fresh tumor biopsies at baseline and an on treatment biopsy are also
mandatory for 10 patients enrolled to Stage 2 of Arm D.

- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 or 1

- Adequate Bone Marrow, Renal, Cardiac, and Liver Function

Exclusion Criteria:

- Patients with known active brain metastases

- Chemotherapy, radiotherapy (other than palliative radiotherapy to lesions that will
not be followed for tumor assessment on this study, ie, non target lesions),
biological or investigational agents within 4 weeks of the start of the study
treatment (6 weeks for mitomycin C or nitrosoureas).

- Any surgery (not including minor procedures such as lymph node biopsy, needle biopsy,
and/or placement of port-a-cath) within 4 weeks of start of the study treatment; or
not fully recovered from any side effects of previous procedures.

- In Arm D only: Patients with glaucoma, intraocular pressure > 21 mmHg, history of
retinal vein occlusions, ocular ischemia or any other clinically significant
abnormality in the ophthalmologic exam which would make the patient inappropriate for
entry into this study

- For patients enrolling in Stage 2 prior therapy with an agent that is known or
proposed to be active by action on PI3K and/or mTOR.

- Prior high dose chemotherapy requiring hematopoietic stem cell transplantation within
12 months of study treatment start.

- Known impaired pulmonary function or demonstrated to be impaired by Pulmonary
Function Test (PFT) for patients who present with clinical suggestion of impairment.

- Uncontrolled or significant cardiovascular disease

- Current use or anticipated need for food or drugs that are known potent CYP3A4
inhibitors

- Current or anticipated need for food or drugs that are known potent CYP3A4 inducers