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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04585750
Recruitment Status : Not yet recruiting
First Posted : October 14, 2020
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
PMV Pharmaceuticals, Inc

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Advanced Malignant Neoplasm Metastatic Cancer Metastatic Solid Tumor Drug: PC14586 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
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
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
Estimated Study Start Date : November 1, 2020
Estimated Primary Completion Date : November 1, 2024
Estimated Study Completion Date : December 15, 2025

Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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 Committee


Secondary Outcome Measures :
  1. 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

  2. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04585750


Contacts
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Contact: PMV Pharma Clinical Study Information Center (609) 235-4038 ext 255 clinicaltrials@pmvpharma.com

Sponsors and Collaborators
PMV Pharmaceuticals, Inc
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Responsible Party: PMV Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT04585750    
Other Study ID Numbers: PMV-586-101
First Posted: October 14, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by PMV Pharmaceuticals, Inc:
PC14586
p53
Y220C
Phase 1
Phase 1/2
PMV
PMV Pharma
p53 mutation
TP53
TP53 mutation
p53 mutant
p53 reactivator
Additional relevant MeSH terms:
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Neoplasms