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

Recruiting now · Phase 1/Phase 2

Conditions studied: 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

In brief

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.

Key facts

Study ID

NCT04585750

Run by

PMV Pharmaceuticals, Inc

People needed

300

Starts

2020-10-29

Expected to finish

2027-12-31

Last updated by the study team

2026-08-10

Who can join

Age: 12 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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)
• Additional Criteria for Inclusion in Phase 1b (rezatapopt) + pembrolizumab combination)
• Anti-PD-1/PD-L1 naive or must have progressed on treatment
• Measurable disease

You may not qualify if…

• Anti-cancer therapy within 21 days (or 5 half-lives) of receiving the study drug
• Radiotherapy within 14 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 within 6 months prior to screening, 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 and strong CYP2C9 inhibitors/inducers within 14 days of first dose of rezatapopt
• 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
• Additional Criteria for Exclusion from Phase 2 (rezatapopt monotherapy)
• Known KRAS mutation, defined as a single nucleotide variant (SNV) (Phase 2)
• Additional Criteria for Exclusion from Phase 1b (rezatapopt) + pembrolizumab combination)
• 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

Where it is running

• University of San Diego Moores Cancer Center — La Jolla, California, United States (enrolling)
• UT Southwest Simmons Cancer Center — Dallas, Texas, United States (enrolling)
• USC Norris Comprehensive Cancer Center — Los Angeles, California, United States (enrolling)
• Rocky Mountain Cancer Center — Denver, Colorado, United States (enrolling)
• New Experimental Therapeutics - NEXT Oncology — Austin, Texas, United States (enrolling)
• Texas Oncology — Bedford, Texas, United States (enrolling)
• University of Miami - Sylvester Comprehensive Cancer Center — Miami, Florida, United States (enrolling)
• Advent Health — Orlando, Florida, United States (enrolling)
• Florida Cancer Specialists South — Port Charlotte, Florida, United States (enrolling)
• Massachusetts General Hospital — Boston, Massachusetts, United States (enrolling)
• Yale Cancer Center — New Haven, Connecticut, United States (enrolling)
• Karmanos Cancer Institute — Detroit, Michigan, United States (enrolling)
• Medical Oncology Hematology Consultants — Newark, Delaware, United States (enrolling)
• UCLA Jonsson Comprehensive Cancer Center — Los Angeles, California, United States (enrolling)
• Memorial Sloan Kettering — New York, New York, United States (enrolling)
• Duke University — Durham, North Carolina, United States (enrolling)
• The Cleveland Clinic Taussig Cancer Center — Cleveland, Ohio, United States (enrolling)
• University of Oklahoma — Oklahoma City, Oklahoma, United States (enrolling)
• Oregon Health & Science University (OHSU) — Portland, Oregon, United States (enrolling)
• Abramson Cancer Center of the University of Pennsylvania — Philadelphia, Pennsylvania, United States (enrolling)
• University of Pittsburgh Medical Center — Pittsburgh, Pennsylvania, United States (enrolling)
• WellSpan York Cancer Center — York, Pennsylvania, United States (enrolling)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (enrolling)
• Sarah Cannon Research Institute — Nashville, Tennessee, United States (enrolling)
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (enrolling)

Full record on ClinicalTrials.gov

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