Ovarian Cancer Clinical Trial

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

Summary

This study will assess the safety, tolerability, and efficacy of multiple dose levels of PC14586 alone and in combination with pembrolizumab in participants with advanced solid tumors containing a TP53 Y220C mutation.

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Full Description

PC14586 (INN: rezatapopt) is a first-in-class, oral, small molecule p53 reactivator that is selective for the TP53 Y220C mutation.

The primary objective of Phase 1 Monotherapy is to establish the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of PC14586 (INN: rezatapopt). Secondary objectives are to characterize the pharmacokinetic (PK) properties, safety and tolerability, and to assess preliminary efficacy including overall response rate (ORR).

The primary objective of Phase 1b Combination Therapy is to establish the MTD/RP2D of PC14586 (INN: rezatapopt) when administered in combination with pembrolizumab. Secondary objectives of Phase 1b Combination Therapy are to characterize PK, safety and tolerability, and to assess preliminary efficacy of PC14586 (INN: rezatapopt) when administered in combination with pembrolizumab, including ORR.

The primary objective of Phase 2 Monotherapy is to evaluate the efficacy of PC14586 (INN: rezatapopt) at the RP2D including the ORR in the Ovarian Cancer Cohort and the ORR across all cohorts as determined by blinded independent central review. Secondary objectives of Phase 2 are to characterize the safety, PK properties, quality of life, and other efficacy measures of PC14586 (INN: rezatapopt) at the RP2D.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

At least 18 years of age or 12 to 17 years of age after Safety Review Committee approval.
Advanced 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 (PC14586 (INN: 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 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 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

Additional Criteria for Exclusion from Phase 2 (PC14586 monotherapy)

Known KRAS mutation, defined as a single nucleotide variant (SNV) (Phase 2)

Additional Criteria for Exclusion from Phase 1b (PC14586 (INN: 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 PC14586 (INN: rezatapopt)

Study is for people with:

Ovarian Cancer

Phase:

Phase 1

Estimated Enrollment:

230

Study ID:

NCT04585750

Recruitment Status:

Recruiting

Sponsor:

PMV Pharmaceuticals, Inc

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There are 24 Locations for this study

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City of Hope
Duarte California, 91010, United States More Info
Stephen Gruber, MD
Contact
University of California, San Diego
La Jolla California, 92093, United States More Info
Shumei Kato, MD
Contact
USC Norris Comprehensive Cancer Center
Los Angeles California, 90033, United States More Info
Anthony El-Khoueiry, MD
Contact
Yale Cancer Center
New Haven Connecticut, 06519, United States More Info
Patricia LoRusso, MD
Contact
University of Miami - Sylvester Comprehensive Cancer Center
Miami Florida, 33136, United States More Info
Gilberto de Lima Lopes Jr., MD
Contact
Florida Cancer Specialists South
West Palm Beach Florida, 33401, United States More Info
Ivor Percent, MD
Contact
Indiana University
Indianapolis Indiana, 46240, United States More Info
Mateusz Opyrchal, MD
Contact
Massachusetts General Hospital
Boston Massachusetts, 02114, United States More Info
Aparna Parikh, MD
Contact
Dana Farber Cancer Institute
Boston Massachusetts, 02215, United States More Info
Geoffrey Shapiro, MD, PhD
Contact
Karmanos Cancer Institute
Detroit Michigan, 48201, United States More Info
Dipesh Uprety, MD
Contact
Roswell Park Comprehensive Cancer Institute
Buffalo New York, 14203, United States More Info
Bailey Fitzgerald, MD
Contact
Memorial Sloan Kettering
New York New York, 10065, United States More Info
Alison Schram, MD
Contact
The Cleveland Clinic Taussig Cancer Center
Cleveland Ohio, 44195, United States More Info
Dale Shepard, MD
Contact
University of Oklahoma
Oklahoma City Oklahoma, 73104, United States More Info
Debra Richardson, MD
Contact
Oregon Health & Science University (OHSU)
Portland Oregon, 97210, United States More Info
Shivaani Kummar, MD
Contact
Abramson Cancer Center of the University of Pennsylvania
Philadelphia Pennsylvania, 19104, United States More Info
Thomas Karasic, MD
Contact
Medical University of South Carolina
Charleston South Carolina, 29425, United States More Info
John Kaczmar, MD
Contact
Sarah Cannon Research Institute
Nashville Tennessee, 37203, United States More Info
Melissa Johnson, MD
Contact
New Experimental Therapeutics - NEXT Oncology
Austin Texas, 78705, United States More Info
Anthony Tolcher, MD
Contact
The University of Texas MD Anderson Cancer Center
Houston Texas, 77030, United States More Info
Escaterina Dumbrava, MD
Contact
New Experimental Therapeutics of San Antonio - NEXT Oncology
San Antonio Texas, 78229, United States More Info
Anthony Tolcher, MD
Contact
Virginia Cancer Specialists
Fairfax Virginia, 22031, United States More Info
Alexander Spira, MD
Contact
University of Washington, Fred Hutchinson Cancer Center
Seattle Washington, 98109, United States More Info
John Thompson, MD
Contact
University of Wisconsin Carbone Cancer Center
Madison Wisconsin, 53705, United States More Info
Nataliya Uboha, MD, PhD
Contact
Chris O'Brien Lifehouse Hospital
Camperdown New South Wales, , Australia More Info
Peter Grimison, MD
Contact
Monash Medical Centre
Clayton Victoria, , Australia More Info
Amy Body, MD
Contact
Linear Clinical Research
Nedlands Western Australia, , Australia More Info
Michael Millward, MD
Contact
ICANS - Institut de cancérologie Strasbourg Europe
Strasbourg Bas-Rhin, , France More Info
Lauriane Eberst, MD
Contact
Institut Bergonie
Bordeaux Gironde, , France More Info
Antoine Italiano, MD
Contact
Institut Claudius Regaud
Toulouse Haute-Garonne, , France More Info
Carlos-Alberto Gomez-Roca, MD
Contact
EDOG Institut de Cancerologie de l'Ouest
Saint-Herblain Loire-Atlantique, , France More Info
Jean-Sebastien Frenel, MD
Contact
Centre Jean Perrin
Clermont-Ferrand Puy-de-Dôme, , France More Info
Xavier Durando, MD
Contact
Institut Gustave Roussy
Villejuif Val-de-Marne, , France More Info
Santiago Ponce Aix, MD
Contact
Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer
Lyon , , France More Info
Isabelle Ray-Coquard, MD
Contact
Nationale Centrum für Tumorerkrankungen (NCT) Heidelberg
Heidelberg Baden-Württemberg, , Germany More Info
Martin Haag, MD
Contact
Universitätsklinikum Augsburg
Augsburg Bayern, , Germany More Info
Rainer Claus, MD
Contact
Universitätsklinikum Frankfurt
Frankfurt Hessen, , Germany More Info
Martin Sebastian, MD
Contact
Universitätsklinikum Essen
Essen Nordrhein-Westfalen, , Germany More Info
Marcel Wiesweg, MD
Contact
Asklepios Klinik Altona
Hamburg , , Germany More Info
Dirk Arnold, MD
Contact
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Rome Lazio, , Italy More Info
Domenica Lorusso, MD
Contact
Istituti Fisioterapici Ospitalieri - Istituto Nazionale Tumori Regina Elena
Rome Lazio, , Italy More Info
Lorenza Landi, MD
Contact
ASST Grande Ospedale Metropolitano Niguarda
Milano Lombardia, , Italy More Info
Salvatore Siena, MD
Contact
Fondazione IRCCS Istituto Nazionale Dei Tumori
Milano Lombardia, , Italy More Info
Massimo Di Nicola, MD
Contact
Istituto Europeo Di Oncologia
Milano Lombardia, , Italy More Info
Giuseppe Curigliano, MD
Contact
Istituto Clinico Humanitas
Rozzano Lombardia, , Italy More Info
Armando Santoro, MD
Contact
Fondazione del Piemonte per l'Oncologia (IRCCS)
Candiolo Torino, , Italy More Info
Vanesa Gregorc, MD
Contact
Asan Medical Center
Seoul , , Korea, Republic of More Info
Dae Ho Lee, MD
Contact
National University Hospital
Kent Ridge , , Singapore More Info
David Shao Peng Tan, MD
Contact
Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON
Barcelona , , Spain More Info
Irene Braña, MD
Contact
NEXT Oncology-Hospital Quironsalud Barcelona
Barcelona , , Spain More Info
Elena Garralda, MD
Contact
START MADRID_Hospital Universitario Fundacion Jimenez Diaz
Madrid , , Spain More Info
Victor Moreno Garcia, MD
Contact
START MADRID_Hospital Universitario HM Sanchinarro - CIOCC
Madrid , , Spain More Info
Maria Jose De Miguel Luken, MD
Contact
Hospital Clinico Universitario de Valencia
Valencia , , Spain More Info
Desamparados Roda Perez, MD
Contact
Sarah Cannon Research Institute UK
London Middlesex, , United Kingdom More Info
Elisa Fontana, MD, PhD
Contact
Royal Victoria Infirmary
Newcastle Upon Tyne Tyne And Wear, , United Kingdom More Info
Alastair Greystoke, MB ChB PhD
Contact

How clear is this clinincal trial information?

Study is for people with:

Ovarian Cancer

Phase:

Phase 1

Estimated Enrollment:

230

Study ID:

NCT04585750

Recruitment Status:

Recruiting

Sponsor:


PMV Pharmaceuticals, Inc

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