An Open-label, Phase I, Dose Escalation Study Evaluating the Safety, Tolerability and Pharmacokinetics of GDC-0623 Administered Daily in Patients With Locally Advanced or Metastatic Solid Tumors

Inclusion Criteria:

- Histologically or cytologically documented, locally advanced or metastatic solid
tumors for which standard therapy either does not exist or has proven ineffective or
intolerable

- Evaluable disease or disease measurable per RECIST

- Life expectancy >= 12 weeks

- Adequate hematologic and end organ function

- Agreement to use effective form of contraception for the duration of the study

- Consent to provide archival tissue

- For the cohort expansion stage (Stage II): Patients in this cohort must have had no
more than four prior systemic therapies for cancer and must have KRAS mutant CRC
(Stage II A and B), pancreatic cancer (Stage IIC, or KRAS mutant NSCLC [Stage IID])

Exclusion Criteria:

- History of prior significant toxicity from a MEK pathway inhibitor requiring
discontinuation of treatment

- History of parathyroid disorder or history of malignancy-associated hypercalcemia
requiring therapy in the last 6 months

- History of retinal vein occlusion (RVO) or predisposing factors to RVO, including
uncontrolled hypertension, uncontrolled diabetes, uncontrolled hyperlipidemia, and
coagulopathy

- Evidence of visible retinal pathology considered a risk factor for retinal vein
thrombosis

- History of glaucoma

- Palliative radiotherapy, experimental therapy, or anti-cancer therapy or major
surgical procedure within a specified timeframe prior to first dose of study drug

- Current severe, uncontrolled systemic disease

- History of clinically significant cardiac dysfunction

- History of active gastrointestinal bleeding within 6 months prior to screening

- Clinically significant history of liver disease, current alcohol abuse, or current
known active infection with HIV, or hepatitis B or C virus

- Active autoimmune disease

- Uncontrolled ascites

- Pregnancy, lactation, or breastfeeding

- Known brain metastases that are untreated, symptomatic, or require therapy to control
symptoms

- For the Exploratory PK Cohorts (Stage IB and Stage IC): Patients who have a history
of or ongoing gastro-esophageal reflux disease or peptic ulcer, or who have gastric
pathology or history of gastric surgery which could affect absorption of GDC-0623
from the stomach, will be excluded from these cohorts