The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a p53 Y220C Mutation
The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a p53 Y220C Mutation
This study will assess the safety and tolerability of multiple dose levels of PC14586 in
 participants with advanced solid tumors containing a p53 Y220C mutation.
PC14586 is a first-in-class, oral, small molecule p53 reactivator that is selective for the
 p53 Y220C mutation. The trial will be conducted in 2 parts: dose escalation (Phase 1) and
 dose expansion (Phase 2).

 The primary objective of Phase 1 is to establish the maximum tolerated dose / recommended
 dose of PC14586 to treat participants with advanced solid tumors harboring a p53 Y220C
 mutation. Secondary objectives of Phase 1 are to characterize the pharmacokinetic properties
 of the investigational drug, its safety and tolerability, and to assess the overall response
 rate (ORR).

 The primary objective of Phase 2 is to assess the ORR in participants with advanced solid
 tumors harboring a p53 Y220C mutation as determined by an independent radiology committee.
 Secondary objectives of Phase 2 include the safety, pharmacokinetic properties, and efficacy
 of PC14586 at the recommended dose.
Inclusion Criteria:

 -  At least 18 years of age or 12 to 17 years of age after adequate adult safety data
 become available

 -  Advanced solid malignancy with a p53 Y220C mutation

 -  Eastern Cooperative Oncology Group (ECOG) status of 0 or 1

 -  Previously treated with one or more lines of anticancer therapy and progressive
 disease

 -  Adequate organ function

 Exclusion Criteria:

 -  Anti-cancer therapy within 21 days (or 5 half-lives) of receiving the study drug

 -  Radiotherapy within 28 days of receiving the study drug

 -  Primary CNS tumor

 -  History of leptomeningeal disease or spinal cord compression

 -  Brain metastases, unless asymptomatic and not requiring steroids for at least 2 weeks
 prior to receiving the study drug

 -  Stroke or transient ischemic attack within 6 months prior to screening

 -  Heart conditions such as unstable angina, uncontrolled hypertension, a heart attack
 within 6 months prior to screening, congestive heart failure, prolongation of QT
 interval, or other rhythm abnormalities

 -  Strong CYP3A4 inhibitors or inducers, medications with a known risk of QT/QTc
 prolongation, or proton pump inhibitors

 -  History of gastrointestinal (GI) disease that may interfere with absorption of study
 drug or patients unable to take oral medication

 -  History of prior organ transplant

 -  Known, active malignancy, except for treated cervical intraepithelial neoplasia, or
 non-melanoma skin cancer

 -  Known, active uncontrolled Hepatitis B, Hepatitis C, or human immunodeficiency virus
 infection