phase 1 study of plx7486 as single agent in patients with advanced solid tumors

Conditions: Solid Tumor; Tumors of Any Histology With Activating Trk (NTRK) Point or NTRK Fusion Mutations; Tenosynovial Giant Cell Tumor

Summary: 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.

Eligibility criteria:
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

Keywords: solid tumors activating ntrk point or fusion mutations tenosynovial giant cell tumor tgct