A Study of the Safety, Tolerability, and Effects of Cobimetinib and GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors
Condition: Non-Small Cell Lung Cancer, Metastatic Colorectal Cancer, Metastatic Non Small Cell Lung Cancer, Metastatic Cancers, Melanoma
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Cobimetinib; GDC-0994
Intervention description: Cobimetinib given concurrently or intermittently with GDC-0994 for 21 consecutive days followed by 7 days off.; GDC-0994 given for 21 consecutive days followed by 7 days off, along with concurrent or intermittent dosing of cobimetinib.
Intervention MeSH terms: Ravoxertinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a two-stage dose-escalation study to assess the safety, tolerability and effects of
      oral dosing of cobimetinib and GDC-0994 administered in combination in patients with
      histologically confirmed, locally advanced, or metastatic solid tumors for which standard
      therapies either do not exist or have proven ineffective or intolerable.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  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

          -  Life expectancy > or = 12 weeks

          -  Adequate hematologic and end organ function

          -  For female patients of childbearing potential and male patients with partners of
             childbearing potential, use of an effective form of contraception with continued use
             for study duration and up to 3 months or more following discontinuation of treatment
             drug

          -  Fluorodeoxyglucose positron emission tomography (FDG-PET) avid disease on baseline
             scan

        For enrollment in part 2, patients must meet all of the following:

          -  Measurable disease

          -  No more than four prior systemic therapies for locally advanced or metastatic cancer

        Exclusion Criteria:

          -  History of prior significant toxicity from another MEK inhibitor or ERK inhibitor
             requiring discontinuation of treatment

          -  Evidence of visible retinal pathology as assessed by ophthalmologic examination that
             is considered a risk factor for retinal vein thrombosis

          -  History of glaucoma

          -  Intraocular pressure > 21 mmHg as measured by tonometry

          -  Predisposing factors to retinal vein occlusion (RVO)

          -  History of RVO, neurosensory retinal detachment, or neovascular macular degeneration

          -  Allergy or hypersensitivity to components of the cobimetinib or GDC-0994 formulation

          -  Palliative radiotherapy within 2 weeks prior to first dose of study-drug treatment in
             Cycle 1

          -  Experimental therapy within 4 weeks prior to first dose of study-drug treatment in
             Cycle 1

          -  Major surgical procedure or significant traumatic injury within 4 weeks prior to the
             first dose of study-drug treatment in Cycle 1, or anticipation of the need for major
             surgery during the course of study treatment

          -  Anti-cancer therapy within 28 days prior to the first dose of study-drug treatment in
             Cycle 1

          -  Current severe, uncontrolled systemic disease

          -  History of clinically significant cardiac dysfunction

          -  History of symptomatic congestive heart failure or serious cardiac arrhythmia
             requiring treatment

          -  History of myocardial infarction within 6 months prior to the first dose of study-drug
             treatment in Cycle 1

          -  History of congenital long QT syndrome or QTc > 470 msec

          -  LVEF

          -  History of malabsorption or other condition that would interfere with enteral
             absorption

          -  Clinically significant history of liver disease, current alcohol abuse, or current
             known active infection with HIV, hepatitis B virus, or hepatitis C virus

          -  Any condition requiring warfarin or thrombolytic anticoagulants

          -  Active autoimmune disease

          -  Uncontrolled ascites requiring weekly large volume paracentesis for 3 consecutive
             weeks prior to enrollment

          -  Pregnancy, lactation, or breastfeeding

          -  Known brain metastases that are untreated, symptomatic, or require therapy to control
             symptoms

          -  No other history of or ongoing malignancy that would potentially interfere with the
             interpretation of the Pharmacodynamic (PD) or efficacy assays