Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 12 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 (Phase 1, Phase 2 Cohort A) - History of leptomeningeal disease or spinal cord compression - Brain metastases, unless neurologically stable and do not require steroids to treat associated neurological symptom - 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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
During Phase 1 (Dose Escalation), participants will be assigned a dose level using an accelerated titration design in the initial dose cohorts, followed by a modified toxicity probability interval (mTPI) design in subsequent dose cohorts. A Recommended Phase 2 Dose (RP2D) will be selected at the end of Phase 1 and in Phase 2 (Dose Expansion) the RP2D will be assigned to all participants.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase 1 Dose Escalation
Multiple dose levels of PC14586 will be evaluated in an escalating manner, to determine the maximum tolerated dose and to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of PC14586 to recommend a Phase 2 dose (RP2D).
  • Drug: PC14586
    PC14586 is a first-in-class, oral, small molecule p53 reactivator that is selective for the p53 Y220C mutation, being developed for the treatment of patients with advanced solid tumors harboring a p53 Y220C mutation. PC14586 will be administered orally on a continuous regimen.
Experimental
Phase 2 Dose Expansion, Cohort A
Additional (expansion of) participants will enroll at the RP2D of PC14586 for continued evaluation. Cohort A participants will have advanced solid tumors harboring a p53 Y220C mutation who meet all eligibility criteria and have measureable disease per RECIST 1.1.
  • Drug: PC14586
    PC14586 is a first-in-class, oral, small molecule p53 reactivator that is selective for the p53 Y220C mutation, being developed for the treatment of patients with advanced solid tumors harboring a p53 Y220C mutation. PC14586 will be administered orally on a continuous regimen.
Experimental
Phase 2 Dose Expansion, Cohort B
Additional (expansion of) participants will enroll at the RP2D of PC14586 for continued evaluation. Cohort B participants will have advanced solid tumors harboring a p53 Y220C mutation who do not meet all eligibility criteria (e.g. have a primary central nervous system (CNS) tumor) and do not have measurable disease per RECIST 1.1.
  • Drug: PC14586
    PC14586 is a first-in-class, oral, small molecule p53 reactivator that is selective for the p53 Y220C mutation, being developed for the treatment of patients with advanced solid tumors harboring a p53 Y220C mutation. PC14586 will be administered orally on a continuous regimen.

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Aparna Parikh, MD

More Details

Status
Recruiting
Sponsor
PMV Pharmaceuticals, Inc

Study Contact

PMV Pharma Clinical Study Information Center
(609) 235-4038
clinicaltrials@pmvpharma.com

Detailed Description

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 blinded independent central review. Secondary objectives of Phase 2 include the safety, pharmacokinetic properties, and efficacy of PC14586 at the recommended dose.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.