RECRUITING

The Evaluation of PC14586 in Patients with Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The Phase 2 monotherapy portion of this study is currently enrolling and will evaluate the efficacy and safety of PC14586 (INN rezatapopt) in participants with locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation. The Phase 1 portion of the study will assess the safety, tolerability and preliminary efficacy of multiple dose levels of rezatapopt as monotherapy and in Phase 1b in combination with pembrolizumab.

Official Title

A Phase 1/2 Open-label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of PC14586 in Patients with Locally Advanced or Metastatic Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)

Quick Facts

Study Start:2020-10-29
Study Completion:2026-07-14
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT04585750

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:CHILD, ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * At least 18 years of age or 12 to 17 years of age after Safety Review Committee approval.
  2. * Locally advanced or metastatic solid malignancy with a TP53 Y220C mutation
  3. * Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
  4. * Previously treated with one or more lines of anticancer therapy and progressive disease
  5. * Adequate organ function
  6. * Measurable disease per RECIST v1.1 (Phase 2)
  7. * Anti-PD-1/PD-L1 naive or must have progressed on treatment
  8. * Measurable disease
  1. * Anti-cancer therapy within 21 days (or 5 half-lives) of receiving the study drug
  2. * Radiotherapy within 28 days of receiving the study drug
  3. * Primary CNS tumor
  4. * History of leptomeningeal disease or spinal cord compression
  5. * Brain metastases, unless neurologically stable and do not require steroids to treat associated neurological symptoms
  6. * Stroke or transient ischemic attack within 6 months prior to screening
  7. * 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
  8. * Strong CYP3A4 inducers
  9. * History of gastrointestinal (GI) disease that may interfere with absorption of study drug or patients unable to take oral medication
  10. * History of prior organ transplant
  11. * Known, active malignancy, except for treated cervical intraepithelial neoplasia, or non-melanoma skin cancer
  12. * Known, active uncontrolled Hepatitis B, Hepatitis C, or human immunodeficiency virus infection
  13. * Known KRAS mutation, defined as a single nucleotide variant (SNV) (Phase 2)
  14. * Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor and discontinued from that treatment due to a Grade 3 or higher immune-related AE (irAE)
  15. * Received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention
  16. * Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy within 7 days prior to the first dose of study drug
  17. * Hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
  18. * Active autoimmune disease that has required systemic treatment in past 2 years
  19. * History of radiation pneumonitis
  20. * History of (non-infectious) or active pneumonitis / interstitial lung disease that required steroids
  21. * Active infection requiring systemic therapy
  22. * Known history of HIV infection
  23. * Has previously received rezatapopt

Contacts and Locations

Study Contact

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

Principal Investigator

Marc Fellous, MD
STUDY_DIRECTOR
Sr. Vice President of Medical Affairs

Study Locations (Sites)

Hoag Cancer Center
Irvine, California, 92618
United States
University of California Irvine Chao Family Comprehensive Cancer Center
Irvine, California, 92868
United States
UCLA Jonsson Comprehensive Cancer Center
Los Angeles, California, 90024
United States
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
United States
University of San Francisco
San Francisco, California, 94143
United States
Rocky Mountain Cancer Center
Denver, Colorado, 80218
United States
Yale Cancer Center
New Haven, Connecticut, 06519
United States
University of Miami - Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
United States
Florida Cancer Specialists South
West Palm Beach, Florida, 33401
United States
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, 60611
United States
Indiana University
Indianapolis, Indiana, 46240
United States
Massachusetts General Hospital
Boston, Massachusetts, 02114
United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
United States
Karmanos Cancer Institute
Detroit, Michigan, 48201
United States
Memorial Sloan Kettering
New York, New York, 10065
United States
Duke University
Durham, North Carolina, 27705
United States
The Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, 44195
United States
University of Oklahoma
Oklahoma City, Oklahoma, 73104
United States
Oregon Health & Science University (OHSU)
Portland, Oregon, 97210
United States
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
United States
Medical University of South Carolina
Charleston, South Carolina, 29425
United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
United States
Vanderbilt University Medical Center - Ingram Cancer Center
Nashville, Tennessee, 37232
United States
New Experimental Therapeutics - NEXT Oncology
Austin, Texas, 78705
United States
UT Southwest Simmons Cancer Center
Dallas, Texas, 75390
United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
United States
New Experimental Therapeutics of San Antonio - NEXT Oncology
San Antonio, Texas, 78229
United States
Virginia Cancer Specialists
Fairfax, Virginia, 22031
United States
University of Washington, Fred Hutchinson Cancer Center
Seattle, Washington, 98109
United States
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53705
United States

Collaborators and Investigators

Sponsor: PMV Pharmaceuticals, Inc

  • Marc Fellous, MD, STUDY_DIRECTOR, Sr. Vice President of Medical Affairs

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-10-29
Study Completion Date2026-07-14

Study Record Updates

Study Start Date2020-10-29
Study Completion Date2026-07-14

Terms related to this study

Keywords Provided by Researchers

  • PC14586
  • p53
  • Y220C
  • Phase 1
  • Phase 1/2
  • PMV
  • PMV Pharma
  • p53 mutation
  • TP53
  • TP53 mutation
  • p53 mutant
  • p53 reactivator
  • pembrolizumab
  • Keytruda
  • combination
  • PD-1
  • PD-L1
  • anti-PD-1
  • Merck
  • MSD
  • IgG4
  • mAb
  • Phase 1b
  • NGS
  • Next Generation Sequencing
  • precision
  • Phase 2
  • Rezatapopt

Additional Relevant MeSH Terms

  • Advanced Solid Tumor
  • Advanced Malignant Neoplasm
  • Metastatic Cancer
  • Metastatic Solid Tumor
  • Lung Cancer
  • Ovarian Cancer
  • Endometrial Cancer
  • Prostate Cancer
  • Colorectal Cancer
  • Breast Cancer
  • Other Cancer
  • Locally Advanced
  • Head and Neck Cancer
  • Gall Bladder Cancer
  • Small Cell Lung Cancer
  • Small Cell Lung Cancer ( SCLC )
  • Small Cell Lung Carcinoma
  • NSCLC
  • NSCLC (non-small Cell Lung Cancer)
  • SCLC
  • Non-Small Cell Lung Carcinoma
  • Triple Negative Breast Cancer
  • TNBC
  • HER2+ Breast Cancer
  • Non-Small Cell Lung Cancer
  • ER/PR Positive Breast Cancer
  • HER2- Breast Cancer
  • HER2-positive Breast Cancer
  • HER2-negative Breast Cancer
  • ER/PR(+), Her2(-) Breast Cancer