A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0973 in Combination With GDC-0068 When Administered in Participants With Locally Advanced or Metastatic Solid Tumors

A Phase Ib, Open-Label, Dose-Escalation Study of the Safety, Tolerability and Pharmacokinetics of GDC-0973 and GDC-0068 in Patients With Locally Advanced or Metastatic Solid Tumors

This open-label, multicenter, Phase Ib dose-escalation study will evaluate the safety, tolerability and pharmacokinetics of oral dosing of GDC-0973 and GDC-0068 administered in combination in patients with locally advanced or metastatic solid tumors. Cohorts of patients will receive multiple ascending doses of GDC-0973 and GDC-0068. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Inclusion Criteria:

• Histologically or cytologically documented locally advanced or metastatic solid tumors for which standard therapies either do not exist or have proven ineffective or intolerable
• Evaluable disease or disease measurable per Response Evaluation Criteria in Solid Tumors (RECIST)
• Life expectancy >/= 12 weeks
• Adequate hematologic and end organ function

Exclusion Criteria:

• History of prior significant toxicity from another MEK pathway inhibitor requiring discontinuation of treatment
• History of prior significant toxicity from another phosphoinositide 3-kinase (PI3K) or Akt pathway or mammalian target of rapamycin (mTOR) inhibitor requiring discontinuation of treatment
• Anti-cancer therapy within 28 days prior to first dose of study drug, except as stated in protocol
• History of type I or type II diabetes mellitus requiring insulin
• Current severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease)
• Clinically significant history of liver disease, current alcohol abuse, or current known active infection with HIV, hepatitis B or hepatitis C virus
• Active autoimmune disease
• Pregnant or lactating women
• Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms
• History of glaucoma
• History of retinal vein occlusion