A PhaseI Study of HL-085 Plus Vemurafenib in Solid Tumor With BRAF V600 Mutation

Study Overview
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Brief Summary
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This is a phase I, open-label, dose escalation study to evaluate tolerability, safety, pharmacokinetics and efficacy in patients with BRAF V600 mutant advanced solid tumor by HL-085 plus Vemurafenib treatment.

Official Title
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A Phase I, Single Arm, Dose Escalation Study to Evaluate Safety, Pharmacokinetics and Preliminary Efficacy of HL-085 Plus Vemurafenib in Patients With BRAF V600 Mutant Advanced Solid Tumor

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: HL-085
* Drug: Vemurafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BRAF V600 mutation in solid tumor. One measurable lesion as defined by RECIST 1.1 criteria for solid tumors. Chemotherapy, immunotherapy or radiotherapy ≥ 4 weeks prior to starting the study treatment. Surgery (except for tumor biopsy) or severe trauma ≤ 14 days prior to starting the study treatment. ECOG performance status of 0-1. Life expectancy ≥ 3 months. Ability to take the medicine orally. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Hypersensitivity to study drug ingredients or their analogues. Prior therapy with MEK-inhibitor. Receiving any other anti-cancer therapy at the same time . Active central nervous system (CNS) lesion. Bleeding symptoms at Grade 3 within 4 weeks prior to starting study treatment. ECG QTcB≥480msec in screening, or history of congenital long QT syndrome； Uncontrolled concomitant diseases or infectious diseases. Retinal diseases (Retinal Vein Occlusion (RVO) or Retinal pigment epithelial detachment (RPED) , et al.). History of HIV,HCV,HBV infection. Interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis will be excluded. Serum HCG test is positive. Other conditions that increase the risk of study and influence the result.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Sequential Assignment
Interventional Model Description: If no Dose-limiting toxicity (DLT) occurs in the first three subjects in Cycle 1, the dose will be escalated to the next dose level; If a DLT occurs in one of the first three subjects, three additional subjects will be enrolled for the same dose cohort, and undergo the same procedures. Dose -escalation is performed based on the scheduled dose groups until DLT occurs in two or more subjects in a dose group which consists of 3 or 6 subjects.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HL-085 plus Vemurafenib<br>HL-085 will be administered as BID with specified dose. And the Vemurafenib will be taken as the instruction in the label ( 960 mg, BID) | Drug: HL-085<br>* HL-085 ( Capsule) is one MEK inhibitor.<br>Drug: Vemurafenib<br>* Vemurafenib ( Tablet) is BRAF inhibitor,<br>* Other names: ZELBORAF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events | Number of Treatment-Related Adverse Events as Assessed by CTCAE v4.03 will be counted. | up to 12 mouths |