The goal of this clinical research study is to learn how PLX9486 may affect cancer cells with
certain mutations in the KIT gene, specifically in patients with types of advanced solid
tumors including Gastrointestinal Stromal Tumor (GIST).
PLX9486 is designed to block KIT gene mutations. These mutations can cause cancer and cancer
cell growth. By blocking these mutations, the drug may kill the cancer cells with the
mutation and/or stop the tumor from growing. By combining PLX9486 with PLX3397 and PLX9486
with Sunitinib, the investigators hope to block most gene mutations in KIT.
- Male or female ≥ 18 years old
- Part 1 and Part 2b: Patients with advanced solid tumors who have tumor progression
following standard therapy, have treatment-refractory disease, or for whom there is no
effective standard of therapy
- Part 2a and Part 2c: Histologically confirmed locally advanced, metastatic and/or
- Women of child-bearing potential must have a negative pregnancy test within 7 days
prior to initiation of dosing and must agree to use an acceptable method of birth
control from the time of the negative pregnancy test up to 3 months after the last
dose of study drug, Fertile men must also agree to use an acceptable method of birth
control while on study drug and up to 3 months after the last dose of study drug.
- All associated toxicity from previous or concurrent cancer therapy must be resolved
(to ≤ Grade 1 or Baseline) prior to study treatment administration.
- Patients with stable, treated brain metastases are eligible for this trial.
- Willing and able to provide written informed consent prior to any study related
procedures and to comply with all study requirements
- ECOG Performance Status 0-2
- Life expectancy ≥ 3 months
- Adequate hematologic, hepatic, and renal function
- Left ventricular ejection fraction (LVEF) >50% per echocardiogram or MUGA for patients
on the sunitinib arms
- Use of any approved tyrosine kinase inhibitors or investigational agents within 2
weeks or 6 half-lives of the agent, whichever is shorter, prior to receiving study
drugs. Treatment-related adverse events must have resolved or reduced to Grade 1 prior
- Presence of symptomatic or uncontrolled brain or central nervous system metastases.
Patients with stable, treated brain metastases are eligible for this trial. However,
patients must not have required steroid treatment for their brain metastases within 30
days of Screening.
- Known or suspected allergy to the investigational agent or any agent given in
association with this trial
- Clinically significant cardiac arrhythmias including bradyarrhythmias and/or patients
who require anti-arrhythmic therapy (excluding beta blockers or digoxin).
- Congenital long QT syndrome or patients taking concomitant medications known to
prolong the QT interval
- History of clinically significant cardiac disease or congestive heart failure > New
York Heart Association (NYHA) class 2. Patients must not have unstable angina (anginal
symptoms at rest) or new-onset angina within the last 3 months or myocardial
infarction within the past 6 months.
- Hypertension as defined by systolic blood pressure > 140 mmHg or diastolic blood
pressure > 95 mmHg despite optimal medical management
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident
(including transient ischemic attacks), deep vein thrombosis or pulmonary embolism
within the 6 months before start of study medication (except for adequately treated
catheter-related venous thrombosis occurring more than 1 month before the start of
- Inability to take oral medication
- Refractory nausea and vomiting, malabsorption, or significant small bowel resection
that, in the opinion of the Investigator, would preclude adequate absorption
- QTcF ≥ 450 msec (for males) or ≥ 470 msec (for females) at Screening
- Ongoing infection ≥ Grade 2
- Non-healing wound, ulcer, or bone fracture
- Known HIV-positive individuals on combination antiretroviral therapy
- Patients with known active hepatitis B or C, or chronic hepatitis B or C requiring
treatment with antiviral therapy
- Interstitial lung disease with ongoing signs and symptoms at the time of informed
- Pregnant or lactating females
- Presence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol
- Strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives, whichever is
longer, before start of study drug.
- Patients with > Grade 1 (high or low) serum potassium, magnesium, or calcium levels
- Other than the primary malignancy, active cancer (either concurrent or within the last
3 years) that requires non-surgical therapy (e.g., chemotherapy or radiation therapy),
with the exception of surgically treated basal or squamous cell carcinoma of the skin,
melanoma in-situ, or carcinoma in-situ of the cervix
- Major surgery or significant traumatic injury within 14 days prior to Cycle 1 Day 1
- Chemotherapy within 14 days prior to Cycle 1 Day 1
- Biological therapy within 14 days prior to Cycle 1 Day 1
- Radiation therapy within 14 days prior to Cycle 1 Day 1
- Uncontrolled illness or concurrent condition that, in the opinion of the Investigator,
would interfere with the study endpoints or the patient's ability to participate
- Known or demonstrated wild type KIT or PDGF-R, or known or demonstrated mutations of
PDGF‑R, SDH, or NF‑1 causative for the observed malignancy