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The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a p53 Y220C Mutation

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ClinicalTrials.gov Identifier: NCT04585750
Recruitment Status : Recruiting
First Posted : October 14, 2020
Last Update Posted : October 8, 2021
Sponsor:
Information provided by (Responsible Party):
PMV Pharmaceuticals, Inc

Tracking Information
First Submitted Date  ICMJE October 1, 2020
First Posted Date  ICMJE October 14, 2020
Last Update Posted Date October 8, 2021
Actual Study Start Date  ICMJE October 29, 2020
Estimated Primary Completion Date November 1, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 1, 2021)
  • Determine the number and type of adverse events to characterize the safety of PC14586 [ Time Frame: 48 months for study (Phase 1 and 2) ]
    Number of participants with treatment related adverse events
  • Establish the maximum tolerated dose (MTD) (Phase 1) [ Time Frame: The first 21 days of treatment (Cycle 1) per patient ]
    Incidence of dose limiting toxicities (DLTs) during the first 21-day cycle of PC14586
  • Establish the Recommended Phase 2 Dose (RP2D) (Phase 1) [ Time Frame: 20 months for study (end of Phase 1) ]
    RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data
  • Response rate assessment to evaluate the clinical activity / efficacy of PC14586 (Phase 2) [ Time Frame: 48 months for study (Phase 1 and 2) ]
    Overall response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 as assessed by independent review
Original Primary Outcome Measures  ICMJE
 (submitted: October 7, 2020)
  • Characterize the safety of PC14586 [ Time Frame: 48 months for study (Phase 1 and 2) ]
    Number of participants with treatment related adverse events
  • Establish the maximum tolerated dose (MTD) (Phase 1) [ Time Frame: The first 21 days of treatment (Cycle 1) per patient ]
    Incidence of dose limiting toxicities (DLTs) during the first 21-day cycle of PC14586
  • Evaluate clinical activity / efficacy of PC14586 (Phase 2) [ Time Frame: 48 months for study (Phase 1 and 2) ]
    Overall response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 as assessed by Independent Review Committee
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2020)
  • Blood plasma assessment to characterize the pharmacokinetics (PK) of PC14586 and metabolites (Phase 1 and 2) [ Time Frame: Approximately 12 months per patient (48 months for study) ]
    Blood plasma concentration
  • Response rate assessment to assess clinical activity / efficacy of PC14586 (Phase 1) [ Time Frame: 20 months for study (end of Phase 1) ]
    Overall response rate in accordance with Response Evaluation Criteria in Solid Tumors
Original Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2020)
  • Characterise the pharmacokinetics (PK) of PC14586 and metabolites (Phase 1 and 2) [ Time Frame: Approximately 12 months per patient (48 months for study) ]
    Blood plasma concentration
  • Assess clinical activity / efficacy of PC14586 (Phase 1) [ Time Frame: 20 months for study (end of Phase 1) ]
    Overall response rate in accordance with Response Evaluation Criteria in Solid Tumors
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a p53 Y220C Mutation
Official Title  ICMJE 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
Brief Summary 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 blinded independent central review. Secondary objectives of Phase 2 include the safety, pharmacokinetic properties, and efficacy of PC14586 at the recommended dose.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Solid Tumor
  • Advanced Malignant Neoplasm
  • Metastatic Cancer
  • Metastatic Solid Tumor
Intervention  ICMJE 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.
Study Arms  ICMJE
  • 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).
    Intervention: Drug: PC14586
  • 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.
    Intervention: Drug: PC14586
  • 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.
    Intervention: Drug: PC14586
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 7, 2020)
130
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 15, 2025
Estimated Primary Completion Date November 1, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: PMV Pharma Clinical Study Information Center (609) 235-4038 clinicaltrials@pmvpharma.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04585750
Other Study ID Numbers  ICMJE PMV-586-101
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party PMV Pharmaceuticals, Inc
Study Sponsor  ICMJE PMV Pharmaceuticals, Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account PMV Pharmaceuticals, Inc
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP