Clinical Trials /

This Study Will Evaluate PC14586 in Patients With Advanced Solid Tumors Harboring a p53 Y220C Mutation

NCT04585750

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: This Study Will Evaluate PC14586 in Patients With Advanced Solid Tumors Harboring a p53 Y220C Mutation
  • Official Title: A Phase 1/2 Open-label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of PC14586 in Patients With Advanced Solid Tumors Harboring a p53 Y220C Mutation

Clinical Trial IDs

  • ORG STUDY ID: PMV-586-101
  • NCT ID: NCT04585750

Conditions

  • Advanced Solid Tumor
  • Advanced Malignant Neoplasm
  • Metastatic Cancer
  • Metastatic Solid Tumor

Interventions

DrugSynonymsArms
PC14586Phase 1 Dose Escalation

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.

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 an independent radiology committee.
      Secondary objectives of Phase 2 include the safety, pharmacokinetic properties, and efficacy
      of PC14586 at the recommended dose.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1 Dose EscalationExperimentalMultiple 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).
  • PC14586
Phase 2 Dose Expansion, Cohort AExperimentalAdditional (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.
  • PC14586
Phase 2 Dose Expansion, Cohort BExperimentalAdditional (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.
  • PC14586

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Characterize the safety of PC14586
Time Frame:48 months for study (Phase 1 and 2)
Safety Issue:
Description:Number of participants with treatment related adverse events

Secondary Outcome Measures

Measure:Characterise the pharmacokinetics (PK) of PC14586 and metabolites (Phase 1 and 2)
Time Frame:Approximately 12 months per patient (48 months for study)
Safety Issue:
Description:Blood plasma concentration
Measure:Assess clinical activity / efficacy of PC14586 (Phase 1)
Time Frame:20 months for study (end of Phase 1)
Safety Issue:
Description:Overall response rate in accordance with Response Evaluation Criteria in Solid Tumors

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:PMV Pharmaceuticals, Inc

Trial Keywords

  • PC14586
  • p53
  • Y220C
  • Phase 1
  • Phase 1/2
  • PMV
  • PMV Pharma
  • p53 mutation
  • TP53
  • TP53 mutation
  • p53 mutant
  • p53 reactivator

Last Updated

October 7, 2020