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

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.

Conditions

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

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Study Overview

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Study Details

Study overview

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.

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)

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

Condition
Advanced Solid Tumor
Intervention / Treatment

-

Contacts and Locations

Irvine

Hoag Cancer Center, Irvine, California, United States, 92618

Irvine

University of California Irvine Chao Family Comprehensive Cancer Center, Irvine, California, United States, 92868

Los Angeles

UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California, United States, 90024

Los Angeles

USC Norris Comprehensive Cancer Center, Los Angeles, California, United States, 90033

San Francisco

University of San Francisco, San Francisco, California, United States, 94143

Denver

Rocky Mountain Cancer Center, Denver, Colorado, United States, 80218

New Haven

Yale Cancer Center, New Haven, Connecticut, United States, 06519

Miami

University of Miami - Sylvester Comprehensive Cancer Center, Miami, Florida, United States, 33136

West Palm Beach

Florida Cancer Specialists South, West Palm Beach, Florida, United States, 33401

Chicago

Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, United States, 60611

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.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * At least 18 years of age or 12 to 17 years of age after Safety Review Committee approval.
  • * Locally advanced or metastatic solid malignancy with a TP53 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
  • * Measurable disease per RECIST v1.1 (Phase 2)
  • * Anti-PD-1/PD-L1 naive or must have progressed on treatment
  • * Measurable disease
  • * 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 neurologically stable and do not require steroids to treat associated neurological symptoms
  • * 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 inducers
  • * 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
  • * Known KRAS mutation, defined as a single nucleotide variant (SNV) (Phase 2)
  • * 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)
  • * Received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention
  • * Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy within 7 days prior to the first dose of study drug
  • * Hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
  • * Active autoimmune disease that has required systemic treatment in past 2 years
  • * History of radiation pneumonitis
  • * History of (non-infectious) or active pneumonitis / interstitial lung disease that required steroids
  • * Active infection requiring systemic therapy
  • * Known history of HIV infection
  • * Has previously received rezatapopt

Ages Eligible for Study

12 Years to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

PMV Pharmaceuticals, Inc,

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

Study Record Dates

2026-07-14