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RECRUITING

NCT04585750

PHASE1/PHASE2

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

Sponsor: PMV Pharmaceuticals, Inc

View on ClinicalTrials.gov

Summary

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)

Key Details

Gender

All

Age Range

12 Years - Any

Study Type

INTERVENTIONAL

Enrollment

300

Start Date

2020-10-29

Completion Date

2027-12-31

Last Updated

2026-03-12

Healthy Volunteers

Interventions

DRUG

rezatapopt

First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.

DRUG

pembrolizumab

Participants receive pembrolizumab 200 mg by intravenous (IV) infusion over 30 minutes.

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

Locations (76)

University of California Irvine Chao Family Comprehensive Cancer Center

Irvine, California, United States

University of San Diego Moores Cancer Center

La Jolla, California, United States

UCLA Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Rocky Mountain Cancer Center

Denver, Colorado, United States

Yale Cancer Center

New Haven, Connecticut, United States

Medical Oncology Hematology Consultants

Newark, Delaware, United States

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Advent Health

Orlando, Florida, United States

Florida Cancer Specialists South

Port Charlotte, Florida, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Columbia University

New York, New York, United States

Memorial Sloan Kettering

New York, New York, United States

Duke University

Durham, North Carolina, United States

The Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

University of Oklahoma

Oklahoma City, Oklahoma, United States

Oregon Health & Science University (OHSU)

Portland, Oregon, United States

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

WellSpan York Cancer Center

York, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

New Experimental Therapeutics - NEXT Oncology

Austin, Texas, United States

UTSW - Moody Outpatient Center - Parkland Health

Dallas, Texas, United States

UT Southwest Simmons Cancer Center

Dallas, Texas, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

New Experimental Therapeutics of San Antonio - NEXT Oncology

San Antonio, Texas, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

University of Washington, Fred Hutchinson Cancer Center

Seattle, Washington, United States

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

Chris O'Brien Lifehouse Hospital

Camperdown, New South Wales, Australia

Mater Cancer Care Centre

South Brisbane, Queensland, Australia

Flinders Medical Center

Bedford Park, South Australia, Australia

Monash Medical Centre

Clayton, Victoria, Australia

Linear Clinical Research

Nedlands, Western Australia, Australia

ICANS - Institut de cancérologie Strasbourg Europe

Strasbourg, Bas-Rhin, France

Institut Bergonie

Bordeaux, Gironde, France

Institut Claudius Regaud

Toulouse, Haute-Garonne, France

EDOG Institut de Cancerologie de l'Ouest

Saint-Herblain, Loire-Atlantique, France

Centre Jean Perrin

Clermont-Ferrand, Puy-de-Dôme, France

Institut Gustave Roussy

Villejuif, Val-de-Marne, France

Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer

Lyon, France

CHU de Nîmes

Nîmes, France

Institute Cancer De Lorraine

Vandœuvre-lès-Nancy, France

Nationale Centrum für Tumorerkrankungen (NCT) Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Universitätsklinikum Augsburg

Augsburg, Bavaria, Germany

Asklepios Klinik Altona

Hamburg, Hamburg, Germany

Universitätsklinikum Frankfurt

Frankfurt am Main, Hesse, Germany

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, Germany

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio, Italy

Istituti Fisioterapici Ospitalieri - Istituto Nazionale Tumori Regina Elena

Rome, Lazio, Italy

ASST Grande Ospedale Metropolitano Niguarda

Milan, Lombardy, Italy

Fondazione IRCCS Istituto Nazionale Dei Tumori

Milan, Lombardy, Italy

Istituto Europeo Di Oncologia

Milan, Lombardy, Italy

Istituto Clinico Humanitas

Rozzano, Lombardy, Italy

Fondazione del Piemonte per l'Oncologia (IRCCS)

Candiolo, Torino, Italy

Humanitas San Pio X

Milan, Italy

IRCCS - lstituto Nazionale Tumori - Fondazione G. Pascale

Naples, Italy

National University Hospital

Kent Ridge, Singapore

National Cancer Center of Singapore

Singapore, Singapore

Asan Medical Center

Seoul, South Korea

National Cancer Center

Seoul, South Korea

Samsung Medical Center

Seoul, South Korea

Seoul University Hospital

Seoul, South Korea

Severance Hospital Yonsei University

Seoul, South Korea

START MADRID_Hospital Universitario Fundacion Jimenez Diaz

Madrid, Madrid, Spain

START MADRID_Hospital Universitario HM Sanchinarro - CIOCC

Madrid, Madrid, Spain

Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON

Barcelona, Spain

NEXT Oncology-Hospital Quironsalud Barcelona

Barcelona, Spain

Hospital Universitario 12 de Octubre

Madrid, Spain

START Rioja

Rioja, Spain

Hospital Clinico Universitario de Valencia

Valencia, Spain

Sarah Cannon Research Institute UK

London, Middlesex, United Kingdom

Freeman Hospital

Newcastle upon Tyne, Tyne and Wear, United Kingdom

Clinical Research Directory

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

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (76)