A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0623 in Patients With Locally Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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This is an open-label, multicenter, Phase I dose-escalation study to assess the safety, tolerability, and pharmacokinetics of GDC-0623 in patients with locally advanced or metastatic solid tumors. Patients will be enrolled in one of two stages: a dose-escalation stage (Stage I) followed by an expansion stage (Stage II). Stage I will evaluate the safety, tolerability, and pharmacokinetics of increasing doses of GDC-0623 administered orally on a 21 day on/7-day off dosing schedule.

Official Title
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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

Conditions
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Solid Cancers

Intervention / Treatment
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* Drug: GDC-0623


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: GDC-0623<br>* Repeating oral dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and nature of dose-limiting toxicities (DLTs) |  | Through study completion or early discontinuation | 
| Incidence, nature, and severity of adverse events and serious adverse events, graded according to NCI CTCAE, v4.0 |  | Through study completion or early discontinuation | 
| Pharmacokinetic parameters of GDC-0623 (total exposure, maximum and minimum plasma concentrations, time to maximum plasma concentration, elimination half-life) |  | Through study completion or early discontinuation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response for patients with measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) |  | Through study completion or early discontinuation | 
| Duration of objective response for patients with measurable disease according to RECIST |  | Through study completion or early discontinuation | 
| Progression-free survival (PFS) for patients with measurable disease according to RECIST |  | Through study completion or early discontinuation |