A Phase 1b Open Label, Dose Escalation Study of PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma

Study Overview
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Brief Summary
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The purpose of this research study is to test the safety of an investigational new drug called PLX3397 when used in combination with Vemurafenib (Zelboraf™) at different dose levels. Vemurafenib has been approved by the United States Food and Drug Administration (FDA)/European Medicines Agency (EMA) for the treatment of a specific category of unresectable or metastatic melanoma.

Official Title
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A Phase 1b Open Label, Dose Escalation Study to Assess Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Unresectable or Metastatic Melanoma

Conditions
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V600-mutated BRAF Unresectable Melanoma, V600-mutated BRAF Metastatic Melanoma, Stage III or Stage IV Metastatic Melanoma That Has Not Been Previously Treated With a Selective BRAF Inhibitor

Intervention / Treatment
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* Drug: PLX3397
* Drug: vemurafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥18 years old. Patients with histologically confirmed unresectable Stage III or Stage IV metastatic melanoma who have not been previously treated with a selective BRAF inhibitor. Presence of a BRAF V600 mutation in the tumor tissue using the cobas BRAF mutation assay or comparable standard of care methodology. Measurable disease per RECIST v. 1.1 criteria. ECOG performance status 0 or 1. Exclusion Criteria: Radiation therapy within 14 days of C1D1. Investigational drug use within 28 days of C1D1. Patients with active CNS lesions are excluded (i.e., those with radiographically unstable, symptomatic lesions). However, patients treated with stereotactic therapy or surgery are eligible if they remain without evidence of disease progression in the brain for ≥3 weeks.

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: Dose extension cohort<br>Patients will take PLX3397 and vemurafenib at the recommended phase 2 dose. This will be determined by the tolerability and safety of these drugs in the previous 3 cohorts. | Drug: PLX3397<br> <br> Drug: vemurafenib<br> <br> * Other names: Zelboraf;|
| Experimental: Cohort 3<br>Patients will take 1000mg/day of PLX3397 and 960mg BID of vemurafenib | Drug: PLX3397<br> <br> Drug: vemurafenib<br> <br> * Other names: Zelboraf;|
| Experimental: Cohort 2<br>Patients will take 800mg/day of PLX3397 and 960mg BID of vemurafenib | Drug: PLX3397<br> <br> Drug: vemurafenib<br> <br> * Other names: Zelboraf;|
| Experimental: Cohort 1<br>Patients will take 800mg/day of PLX3397 and 720mg BID of vemurafenib | Drug: PLX3397<br> <br> Drug: vemurafenib<br> <br> * Other names: Zelboraf;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma |  | 1 year |