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

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

• PLX7486 TsOH (Drug): PLX7486 TsOH capsules, 50mg

Primary outcomes

• Safety of PLX7486 as single agent as measured by adverse events and serious adverse events. [1 year]
• Area under the plasma concentration-time curve [AUC0-t, AUC0-inf] [1 year]: Area under the plasma concentration-time curve \[AUC0-t, AUC0-inf\] will be used to assess the pharmacokinetic profile of PLX7486.
• Peak concentration (Cmax) [1 year]: Peak concentration (Cmax) will be used to assess the pharmacokinetic profile of PLX7486.
• Time to peak concentration (Tmax) [1 year]: Time to peak concentration (Tmax) will be used to assess the pharmacokinetic profile of PLX7486.
• Half life (t1/2) [1 year]: Half life (t1/2) will be used to assess the pharmacokinetic profile of PLX7486.
• Terminal elimination rate constant (Kel) [1 year]: Terminal elimination rate constant (Kel) will be used to assess the pharmacokinetic profile of PLX7486.

Secondary outcomes

• Duration of response (DOR) [1 year]: Duration of response is defined as the number of days from the date of initial response (PR or better) to the date of first documented disease progression/relapse or death, whichever occurs first.
• Progression-Free Survival (PFS) [6 month]: Progression-free survival (PFS) is defined as the number of days from start of therapy to the date of documented disease progression/relapse, whichever occurs first.
• Overall Response Rate (ORR) [1year]
• Overall Survival (OS) [1 year]

Sex: All, ages: 18 Years to any

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