Phase 1 Study of PLX7486 as Single Agent in Patients With Advanced Solid Tumors

A Phase 1 Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of PLX7486 as a Single Agent in Patients With Advanced Solid Tumors

The objective of this study is to determine the safety, pharmacokinetics, maximum tolerated dose/recommended Phase 2 dose, and efficacy of PLX7486.

Part 1. Open-label, sequential PLX7486 TsOH single-agent dose escalation in approximately 60 patients with solid tumors.

Inclusion Criteria

• Male or female ≥18 years old

• Patients with histologically confirmed solid tumors who:

  o Part 1: have tumor progression following standard therapy, have treatment-refractory disease, or for whom there is no effective standard of therapy

• Women of child-bearing potential must have a negative pregnancy test within 7 days of initiation of dosing and must agree to use an acceptable method of birth control. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥1 year. 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. However, patients must not have required steroid treatment for their brain metastases within 30 days of Screening.

• Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements

• Karnofsky performance status ≥70%

• Life expectancy ≥3 months

• Adequate hematologic, hepatic, and renal function

Exclusion Criteria

• 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
• Chemotherapy within 28 days prior to C1D1
• Biological therapy within 5 half-lives prior to C1D1
• Radiation therapy within 28 days or 5 half-lives prior to C1D1, whichever is longer
• Investigational drug use within 28 days or 5 half-lives, whichever is longer, prior to C1D1
• Part 1 only: (a) Patients with active or a history of glucose intolerance or diabetes mellitus and (b) Hemoglobin A1c ≥7%
• ≥Grade 2 sensory neuropathy at baseline
• Uncontrolled intercurrent illness (i.e., active infection) or concurrent condition that, in the opinion of the Investigator, would interfere with the study endpoints or the patient's ability to participate
• Refractory nausea and vomiting, malabsorption, small bowel resection that, in the opinion of the Investigator, would preclude adequate absorption
• Mean QTcF ≥450 msec (for males) or ≥470 msec (for females) at Screening
• The presence of a medical or psychiatric condition that, in the opinion of the Principal Investigator, makes the patient inappropriate for inclusion in this study