A Study of PLX3397 in Patients With Unresectable or Metastatic KIT-mutated Melanoma

A Phase I/II Open Label, Multicenter Study of PLX3397 in Patients With Unresectable or Metastatic KIT-mutated Melanoma

The purpose of this Phase I/II study is to evaluate safety, pharmacokinetics, and preliminary efficacy of the investigational drug PLX3397 in subjects with unresectable or metastatic KIT-mutated melanoma.

Inclusion Criteria:

• Age ≥ 18 years
• Unresectable stage III or stage IV melanoma which is histologically confirmed at the treating institution with KIT mutation(s) not known to be resistant to PLX3397
• Presence of measurable lesions by Response Evaluation Criteria in Solid Tumors
• Eastern Cooperative Oncology Group (ECOG) performance Status (PS) 0-2
• Life expectancy ≥ 3 months
• Adequate organ and bone marrow function
• Women of child-bearing potential must have a negative serum pregnancy test at Screening and must agree to use an effective form of contraception from the time of the negative pregnancy test up to 3 months after the last dose of study drug. Women of non-child-bearing potential must have been postmenopausal for ≥ 1 year or surgically sterile.
• Fertile men must agree to use an effective method of birth control during the study and for up to 3 months after the last dose of study drug.
• Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements

Exclusion Criteria:

• Prior treatment with a KIT inhibitor for melanoma
• Presence of NRAS or BRAF mutation
• Exposure to any investigational drug within 28 days or unresolved adverse effects from previous therapy
• Symptomatic brain metastases.
• Active secondary malignancy unless the malignancy is not expected to interfere with the evaluation of safety and is approved by the Sponsor
• Concomitant treatment with other anti-neoplastic agents (hormonal therapy acceptable)
• Uncontrolled intercurrent or infectious illness
• Major surgical procedure or significant traumatic injury within 14 days of initiating study drug or anticipation of the need for major surgery during the study
• Previous radiotherapy to 25% or more of the bone marrow and/or radiation therapy within 28 days prior to study entry
• Inability to swallow capsules, or refractory nausea and vomiting, malabsorption, an external biliary shunt, or significant bowel resection that would preclude adequate absorption
• Congestive heart failure (CHF) New York (NY) Heart Association class III or IV; unstable coronary artery disease [myocardial infarction (MI) more than 6 months prior to study entry is permitted] or serious cardiac arrhythmia
• Baseline QT interval corrected using Fridericia equation (QTcF) ≥ 450 msec (for males) or ≥ 470 msec (for females) at Screening
• Active or chronic infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV)
• Known chronic liver disease
• Women who are breast-feeding or pregnant