La evaluación de PC14586 en pacientes con tumores sólidos avanzados que albergan una mutación p53 Y220C
Un estudio multicéntrico abierto de fase 1/2 para evaluar la seguridad, la tolerabilidad, la farmacocinética, la farmacodinámica y la eficacia de PC14586 en pacientes con tumores sólidos avanzados que albergan una mutación p53 Y220C (PYNNACLE)
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.
Descripción general del estudio
Estado
Condiciones
- Cáncer de mama
- Cáncer de cabeza y cuello
- Carcinoma de pulmón de células pequeñas
- Cáncer de pulmón de células pequeñas
- Cáncer colonrectal
- Cáncer de ovarios
- Cáncer de pulmón de células no pequeñas
- NSCLC
- Cáncer de pulmón
- Cancer de prostata
- Cáncer metastásico
- SCLC
- Cáncer de mama triple negativo
- Tumor sólido avanzado
- Cáncer endometrial
- Tumor sólido metastásico
- Cáncer de mama HER2 positivo
- Cáncer de vesícula biliar
- Cáncer de mama HER2 negativo
- Otro cáncer
- Neoplasia maligna avanzada
- TNBC
- Carcinoma de pulmón de células no pequeñas
- Cáncer de mama HER2+
- NSCLC (cáncer de pulmón de células no pequeñas)
- Localmente avanzado
- Cáncer de pulmón de células pequeñas ( SCLC )
- Cáncer de mama positivo para ER/PR
- ER/PR (+), HER2 (-) Cáncer de mama
- HER2- Cáncer de mama
Intervención / Tratamiento
Descripción detallada
Rezatapopt is a first-in-class, oral, small molecule p53 reactivator that is selective for the TP53 Y220C mutation.
The primary objective of Phase 2 Monotherapy is to evaluate the efficacy of rezatapopt at the Recommended Phase 2 Dose (RP2D) including the Overall Response Rate (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, pharmacokinetic (PK) properties, quality of life, and other efficacy measures of PC14586 rezatapopt at the RP2D. Enrollment is open for the Phase 2 Monotherapy portion of the study.
The primary objective of Phase 1 Monotherapy is to establish the maximum tolerated dose (MTD) and RP2D of rezatapopt. Secondary objectives are to characterize the PK properties, safety and tolerability, and to assess preliminary efficacy including ORR. Enrollment into Phase 1 Monotherapy is complete.
The primary objective of Phase 1b Combination Therapy is to establish the MTD/RP2D of 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 rezatapopt when administered in combination with pembrolizumab, including ORR. Enrollment into Phase 1b Combination Therapy is complete.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Estudio Contacto
- Nombre: PMV Pharma Clinical Study Information Center
- Número de teléfono: (609) 235-4038
- Correo electrónico: clinicaltrials@pmvpharma.com
Ubicaciones de estudio
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Baden-Wurttemberg
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Heidelberg, Baden-Wurttemberg, Alemania
- Reclutamiento
- Nationale Centrum für Tumorerkrankungen (NCT) Heidelberg
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Contacto:
- Martin Haag, MD
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Bavaria
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Augsburg, Bavaria, Alemania
- Reclutamiento
- Universitätsklinikum Augsburg
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Contacto:
- Rainer Claus, MD
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Free and Hanseatic City of Hamburg
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Hamburg, Free and Hanseatic City of Hamburg, Alemania
- Reclutamiento
- Asklepios Klinik Altona
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Contacto:
- Dirk Arnold, MD
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Hesse
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Frankfurt am Main, Hesse, Alemania
- Retirado
- Universitätsklinikum Frankfurt
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North Rhine-Westphalia
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Essen, North Rhine-Westphalia, Alemania
- Reclutamiento
- Universitätsklinikum Essen
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Contacto:
- Marcel Wiesweg, MD
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New South Wales
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Camperdown, New South Wales, Australia
- Reclutamiento
- Chris O'Brien Lifehouse Hospital
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Contacto:
- Peter Grimison, MD
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Queensland
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South Brisbane, Queensland, Australia
- Reclutamiento
- Mater Cancer Care Centre
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Contacto:
- Catherine Shannon, MD
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South Australia
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Bedford Park, South Australia, Australia
- Reclutamiento
- Flinders Medical Center
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Contacto:
- Shawgi Sukumaran, MD
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Victoria
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Clayton, Victoria, Australia
- Reclutamiento
- Monash Medical Centre
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Contacto:
- Sophia Frentzas, MD
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Western Australia
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Nedlands, Western Australia, Australia
- Reclutamiento
- Linear Clinical Research
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Contacto:
- Michael Millward, MD
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Seoul, Corea del Sur
- Reclutamiento
- Samsung Medical Center
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Contacto:
- Chel Hun Choi, MD
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Seoul, Corea del Sur
- Reclutamiento
- Asan Medical Center
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Contacto:
- Dae Ho Lee, MD
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Seoul, Corea del Sur
- Reclutamiento
- Seoul University Hospital
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Contacto:
- Seock-Ah Im, MD
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Seoul, Corea del Sur
- Reclutamiento
- Severance Hospital Yonsei University
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Contacto:
- Jung-Yun Lee, MD
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Seoul, Corea del Sur
- Reclutamiento
- National Cancer Center
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Contacto:
- Myong Cheol Lim, MD, PhD
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Barcelona, España
- Reclutamiento
- NEXT Oncology-Hospital Quironsalud Barcelona
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Contacto:
- Elena Garralda, MD
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Barcelona, España
- Reclutamiento
- Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON
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Contacto:
- Lorena Farinas, MD
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Madrid, España, 28041
- Reclutamiento
- Hospital Universitario 12 de Octubre
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Contacto:
- Santiago Ponce Aix, MD
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Rioja, España
- Reclutamiento
- START Rioja
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Contacto:
- Jorge Luis Ramon Patino, MD
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Valencia, España
- Reclutamiento
- Hospital Clinico Universitario de Valencia
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Contacto:
- José Alejandro Pérez Fidalgo, MD
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Madrid
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Madrid, Madrid, España
- Reclutamiento
- START MADRID_Hospital Universitario Fundacion Jimenez Diaz
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Contacto:
- Victor Moreno Garcia, MD
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Madrid, Madrid, España
- Reclutamiento
- START MADRID_Hospital Universitario HM Sanchinarro - CIOCC
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Contacto:
- Irene Moreno, MD
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California
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Irvine, California, Estados Unidos, 92868
- Retirado
- University of California Irvine Chao Family Comprehensive Cancer Center
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La Jolla, California, Estados Unidos, 92093
- Reclutamiento
- University of San Diego Moores Cancer Center
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Contacto:
- Shumei Kato, MD
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Los Angeles, California, Estados Unidos, 90033
- Reclutamiento
- USC Norris Comprehensive Cancer Center
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Contacto:
- Anthony El-Khoueiry, MD
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Los Angeles, California, Estados Unidos, 90024
- Reclutamiento
- UCLA Jonsson Comprehensive Cancer Center
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Contacto:
- Gottfried Konecny, MD
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Colorado
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Denver, Colorado, Estados Unidos, 80218
- Reclutamiento
- Rocky Mountain Cancer Center
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Contacto:
- Allen Cohn, MD
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Connecticut
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New Haven, Connecticut, Estados Unidos, 06519
- Reclutamiento
- Yale Cancer Center
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Contacto:
- Patricia LoRusso, MD
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Delaware
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Newark, Delaware, Estados Unidos, 19713
- Reclutamiento
- Medical Oncology Hematology Consultants
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Contacto:
- Jamal Misleh, MD
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Florida
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Miami, Florida, Estados Unidos, 33136
- Reclutamiento
- University of Miami - Sylvester Comprehensive Cancer Center
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Contacto:
- Gilberto de Lima Lopes Jr., MD
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Orlando, Florida, Estados Unidos, 32803
- Reclutamiento
- Advent Health
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Contacto:
- Robert Holloway, MD
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Port Charlotte, Florida, Estados Unidos, 33980
- Reclutamiento
- Florida Cancer Specialists South
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Contacto:
- Ivor Percent, MD
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02114
- Reclutamiento
- Massachusetts General Hospital
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Contacto:
- Aparna Parikh, MD
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Boston, Massachusetts, Estados Unidos, 02215
- Reclutamiento
- Dana Farber Cancer Institute
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Contacto:
- Geoffrey Shapiro, MD, PhD
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Michigan
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Detroit, Michigan, Estados Unidos, 48201
- Terminado
- Karmanos Cancer Institute
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New York
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New York, New York, Estados Unidos, 10065
- Reclutamiento
- Memorial Sloan Kettering
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Contacto:
- Alison Schram, MD
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New York, New York, Estados Unidos, 10032
- Aún no reclutando
- Columbia University Medical Center
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Contacto:
- June Hou, MD
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North Carolina
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Durham, North Carolina, Estados Unidos, 27705
- Reclutamiento
- Duke University
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Contacto:
- Niharika Mettu, MD, PhD
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Ohio
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Cleveland, Ohio, Estados Unidos, 44195
- Reclutamiento
- The Cleveland Clinic Taussig Cancer Center
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Contacto:
- Dale Shepard, MD
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Oklahoma
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Oklahoma City, Oklahoma, Estados Unidos, 73104
- Reclutamiento
- University of Oklahoma
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Contacto:
- Debra Richardson, MD
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Oregon
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Portland, Oregon, Estados Unidos, 97210
- Reclutamiento
- Oregon Health & Science University (OHSU)
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Contacto:
- Shivaani Kummar, MD
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19104
- Reclutamiento
- Abramson Cancer Center of the University of Pennsylvania
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Contacto:
- Lainie Martin, MD
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Pittsburgh, Pennsylvania, Estados Unidos, 15213
- Reclutamiento
- University of Pittsburgh Medical Center
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Contacto:
- Sarah Taylor, MD, PhD
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York, Pennsylvania, Estados Unidos, 17403
- Reclutamiento
- WellSpan York Cancer Center
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Contacto:
- Ikechukwu Akunyili, MD
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South Carolina
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Charleston, South Carolina, Estados Unidos, 29425
- Terminado
- Medical University of South Carolina
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37203
- Reclutamiento
- Sarah Cannon Research Institute
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Contacto:
- Melissa Johnson, MD
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Texas
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Austin, Texas, Estados Unidos, 78705
- Reclutamiento
- New Experimental Therapeutics - NEXT Oncology
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Contacto:
- David Sommerhalder, MD
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Bedford, Texas, Estados Unidos, 76022
- Reclutamiento
- Texas Oncology
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Contacto:
- Terrence Wong, MD
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Dallas, Texas, Estados Unidos, 75390
- Reclutamiento
- UT Southwest Simmons Cancer Center
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Contacto:
- David Miller, MD
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Houston, Texas, Estados Unidos, 77030
- Reclutamiento
- The University of Texas MD Anderson Cancer Center
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Contacto:
- Ecaterina Dumbrava, MD
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San Antonio, Texas, Estados Unidos, 78229
- Reclutamiento
- New Experimental Therapeutics of San Antonio - NEXT Oncology
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Contacto:
- David Sommerhalder, MD
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Virginia
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Fairfax, Virginia, Estados Unidos, 22031
- Reclutamiento
- Virginia Cancer Specialists
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Contacto:
- Alexander Spira, MD
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Washington
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Seattle, Washington, Estados Unidos, 98109
- Reclutamiento
- University of Washington, Fred Hutchinson Cancer Center
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Contacto:
- Andrew Coveler, MD
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Wisconsin
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Madison, Wisconsin, Estados Unidos, 53705
- Reclutamiento
- University of Wisconsin Carbone Cancer Center
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Contacto:
- Nataliya Uboha, MD, PhD
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Lyon, Francia
- Reclutamiento
- Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer
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Contacto:
- Isabelle Ray-Coquard, MD
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Nîmes, Francia, 30900
- Reclutamiento
- CHU de Nîmes
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Contacto:
- Frédéric Fiteni, MD, PhD
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Vandœuvre-lès-Nancy, Francia, 54519
- Reclutamiento
- Institute Cancer De Lorraine
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Contacto:
- Aurélien Lambert, MD
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Bas-Rhin
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Strasbourg, Bas-Rhin, Francia
- Reclutamiento
- ICANS - Institut de cancérologie Strasbourg Europe
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Contacto:
- Lauriane Eberst, MD
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Gironde
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Bordeaux, Gironde, Francia
- Reclutamiento
- Institut Bergonie
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Contacto:
- Veronique Debien, MD
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Haute-Garonne
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Toulouse, Haute-Garonne, Francia
- Reclutamiento
- Institut Claudius Regaud
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Contacto:
- Carlos-Alberto Gomez-Roca, MD
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Loire-Atlantique
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Saint-Herblain, Loire-Atlantique, Francia
- Reclutamiento
- EDOG Institut de Cancerologie de l'Ouest
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Contacto:
- Jean-Sebastien Frenel, MD
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Puy-de-Dôme
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Clermont-Ferrand, Puy-de-Dôme, Francia
- Reclutamiento
- Centre Jean Perrin
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Contacto:
- Xavier Durando, MD
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Val-de-Marne
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Villejuif, Val-de-Marne, Francia
- Reclutamiento
- Institut Gustave Roussy
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Contacto:
- Yohann Loriot, MD
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Milan, Italia
- Reclutamiento
- Humanitas San Pio X
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Contacto:
- Domenica Lorusso, MD
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Naples, Italia, 80131
- Reclutamiento
- IRCCS - lstituto Nazionale Tumori - Fondazione G. Pascale
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Contacto:
- Anna Passarelli, MD
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Lazio
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Rome, Lazio, Italia
- Reclutamiento
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
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Contacto:
- Anna Fagotti, MD
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Rome, Lazio, Italia
- Reclutamiento
- Istituti Fisioterapici Ospitalieri - Istituto Nazionale Tumori Regina Elena
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Contacto:
- Lorenza Landi, MD
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Lombardy
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Milan, Lombardy, Italia
- Reclutamiento
- ASST Grande Ospedale Metropolitano Niguarda
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Contacto:
- Salvatore Siena, MD
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Milan, Lombardy, Italia
- Reclutamiento
- Fondazione IRCCS Istituto Nazionale Dei Tumori
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Contacto:
- Massimo Di Nicola, MD
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Milan, Lombardy, Italia
- Reclutamiento
- Istituto Europeo Di Oncologia
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Contacto:
- Giuseppe Curigliano, MD
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Rozzano, Lombardy, Italia
- Reclutamiento
- Istituto Clinico Humanitas
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Contacto:
- Armando Santoro, MD
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Torino
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Candiolo, Torino, Italia
- Reclutamiento
- Fondazione del Piemonte per l'Oncologia (IRCCS)
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Contacto:
- Chiara Lazzari, MD
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Middlesex
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London, Middlesex, Reino Unido
- Reclutamiento
- Sarah Cannon Research Institute UK
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Contacto:
- Elisa Fontana, MD, PhD
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Tyne and Wear
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Newcastle upon Tyne, Tyne and Wear, Reino Unido
- Reclutamiento
- Freeman Hospital
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Contacto:
- Alastair Greystoke, MB ChB PhD
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Kent Ridge, Singapur
- Reclutamiento
- National University Hospital
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Contacto:
- David Shao Peng Tan, MD
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Singapore, Singapur, 168582
- Reclutamiento
- National Cancer Center of Singapore
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Contacto:
- Tira Tan, MD
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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). Exception: Ovarian cancer patients with a known KRAS SNV are permitted.
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Phase 1 Monotherapy Dose Escalation
Multiple dose levels of daily oral rezatapopt will be evaluated in an escalating manner, to determine the maximum tolerated dose and to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of rezatapopt to recommend a Phase 2 dose (RP2D). |
First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.
Otros nombres:
|
|
Experimental: Phase 1b Combination Therapy Dose Escalation, Part 1
Multiple dose levels of daily oral rezatapopt in combination with a stable dose of pembrolizumab (200 mg IV q3 weeks) will be evaluated in an escalating manner, to determine the maximum tolerated dose and to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of PC14586 to recommend a Phase 2 dose (RP2D) of rezatapopt when administered in combination with pembrolizumab. |
First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.
Otros nombres:
Participants receive pembrolizumab 200 mg by intravenous (IV) infusion over 30 minutes.
Otros nombres:
|
|
Experimental: Phase 1b Combination Therapy Dose Expansion, PD(L)-1 naive patients
Additional (expansion of) participants will enroll at the RP2D of daily oral PC14586 (INN: rezatapopt) when administered in combination with pembrolizumab (200 mg IV q3 weeks) for continued evaluation. Participants will have advanced solid tumors harboring a p53 Y220C mutation and are PD(L)-1 naive patients. |
First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.
Otros nombres:
Participants receive pembrolizumab 200 mg by intravenous (IV) infusion over 30 minutes.
Otros nombres:
|
|
Experimental: Phase 1b Combination Therapy Dose Expansion, PD(L)-1 relapsed/refractory patients
Additional (expansion of) participants will enroll at the RP2D of daily oral rezatapopt when administered in combination with pembrolizumab (200 mg IV q3 weeks) for continued evaluation. Participants will have advanced solid tumors harboring a p53 Y220C mutation and are PD(L)-1 relapsed/refractory patients. |
First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.
Otros nombres:
Participants receive pembrolizumab 200 mg by intravenous (IV) infusion over 30 minutes.
Otros nombres:
|
|
Experimental: Phase 2 Monotherapy Dose Expansion, Ovarian Cancer Cohort
Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Ovarian Cancer Cohort participants will have locally advanced or metastatic ovarian cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1. |
First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.
Otros nombres:
|
|
Experimental: Phase 2 Monotherapy Dose Expansion, Lung Cancer Cohort
Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Lung Cancer Cohort participants will have locally advanced or metastatic lung cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1. |
First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.
Otros nombres:
|
|
Experimental: Phase 2 Monotherapy Dose Expansion, Breast Cancer Cohort
Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Breast Cancer Cohort participants will have locally advanced or metastatic breast cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1. |
First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.
Otros nombres:
|
|
Experimental: Phase 2 Monotherapy Dose Expansion, Endometrial Cancer Cohort
Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Endometrial Cancer Cohort participants will have locally advanced or metastatic endometrial cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1. |
First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.
Otros nombres:
|
|
Experimental: Phase 2 Monotherapy Dose Expansion, Other Solid Tumors Cohort
Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Other Solid Tumors Cohort participants will have locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1. |
First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt
Periodo de tiempo: 40 months
|
Number of participants with treatment related adverse events |
40 months
|
|
Phase 1 Monotherapy (Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D)
Periodo de tiempo: 30 months
|
RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data |
30 months
|
|
Phase 1 Monotherapy (Dose Escalation): Establish the maximum tolerated dose (MTD) (Phase 1)
Periodo de tiempo: The first 28 days of treatment (Cycle 1) per patient
|
Incidence of dose limiting toxicities (DLTs) during the first 28 days of treatment with rezatapopt |
The first 28 days of treatment (Cycle 1) per patient
|
|
Phase 1b Combination Therapy (Part 1: Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt when administered in combination with pembrolizumab
Periodo de tiempo: 18 months for treatment arm
|
Number of participants with treatment related adverse events |
18 months for treatment arm
|
|
Phase 1b Combination Therapy (Part 1: Dose Escalation): Establish the maximum tolerated dose (MTD) of rezatapopt when administered in combination with pembrolizumab
Periodo de tiempo: The first 28 days of combination treatment arm (starting on Day -7) per patient
|
Incidence of dose limiting toxicities (DLTs) during the first 28 days of treatment with rezatapopt |
The first 28 days of combination treatment arm (starting on Day -7) per patient
|
|
Phase 1b Combination Therapy (Part 1: Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D) of rezatapopt when administered in combination with pembrolizumab
Periodo de tiempo: 18 months
|
RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data |
18 months
|
|
Phase 1b Combination Therapy (Part 2: Dose Expansion): Determine the number and type of adverse events to characterize the safety of rezatapopt when administered in combination with pembrolizumab
Periodo de tiempo: 12 months for treatment arm
|
Number of participants with treatment related adverse events |
12 months for treatment arm
|
|
Phase 2 Monotherapy (Dose Expansion): Response rate assessment to evaluate the clinical activity / efficacy of rezatapopt
Periodo de tiempo: 34 months
|
Overall response rate in accordance with Response Evaluation Criteria (RECIST) v.1.1 as assessed by independent review across all cohorts |
34 months
|
|
Phase 2 Monotherapy (Dose Expansion): Response rate assessment to evaluate the clinical activity / efficacy of rezatapopt in ovarian cancer patients
Periodo de tiempo: 34 months
|
Overall response rate in accordance with Response Evaluation Criteria (RECIST) v.1.1 as assessed by independent review in the ovarian cancer cohort |
34 months
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Phase 1 Monotherapy: PK profile of rezatapopt - Peak concentration (Cmax)
Periodo de tiempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt |
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
|
Phase 1 Monotherapy: PK profile of rezatapopt - Time of peak concentration (Tmax)
Periodo de tiempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt |
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
|
Phase 1 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve from time zero to time of last sampling timepoint (AUC0-t)
Periodo de tiempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt |
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
|
Phase 1 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve in one dosing interval (AUCtau)
Periodo de tiempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt |
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
|
Phase 1 Monotherapy: PK profile of rezatapopt - Trough observed concentrations (Ctrough/Ctau)
Periodo de tiempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt |
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
|
Phase 1 Monotherapy: Blood plasma assessment to describe the concentration of PC14586 and metabolites when rezatapopt is administered orally.
Periodo de tiempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
Blood plasma concentration |
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
|
Phase 1 Monotherapy (Dose Escalation): Overall Response Rate per RECIST v1.1 or PCWG3 modified RECIST v1.1
Periodo de tiempo: 41 months for study (end of Phase 1)
|
Evaluation of preliminary anti-tumor activity of rezatapopt as a single agent |
41 months for study (end of Phase 1)
|
|
Phase 1 Monotherapy (Dose Escalation): Time to Response per RECIST v1.1 or PCWG3 modified RECIST v1.1
Periodo de tiempo: 41 months for study (end of Phase 1)
|
Evaluation of preliminary anti-tumor activity of rezatapopt as a single agent |
41 months for study (end of Phase 1)
|
|
Phase 1 Monotherapy (Dose Escalation): Duration of Response per RECIST v1.1 or PCWG3 modified RECIST v1.1
Periodo de tiempo: 41 months for study (end of Phase 1)
|
Evaluation of preliminary anti-tumor activity of rezatapopt as a single agent |
41 months for study (end of Phase 1)
|
|
Phase 1 Monotherapy (Dose Escalation): Disease Control Rate per RECIST v1.1 or PCWG3 modified RECIST v1.1
Periodo de tiempo: 41 months for study (end of Phase 1)
|
Evaluation of preliminary anti-tumor activity of rezatapopt as a single agent |
41 months for study (end of Phase 1)
|
|
Phase 1 Monotherapy (Dose Escalation): Progression Free Survival per RECIST v1.1 or PCWG3 modified RECIST v1.1
Periodo de tiempo: 41 months for study (end of Phase 1)
|
Evaluation of preliminary anti-tumor activity of rezatapopt as a single agent |
41 months for study (end of Phase 1)
|
|
Phase 1 Monotherapy (Dose Escalation): Overall Survival
Periodo de tiempo: 41 months for study (end of Phase 1)
|
Evaluation of preliminary anti-tumor activity of rezatapopt as a single agent |
41 months for study (end of Phase 1)
|
|
Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Peak concentration (Cmax)
Periodo de tiempo: Approximately 12 months per patient (30 months for treatment arm)
|
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt |
Approximately 12 months per patient (30 months for treatment arm)
|
|
Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Time of peak concentration (Tmax)
Periodo de tiempo: Approximately 12 months per patient (30 months for treatment arm)
|
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt |
Approximately 12 months per patient (30 months for treatment arm)
|
|
Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Area under the plasma concentration-time curve from time zero to time of last sampling timepoint (AUC0-t)
Periodo de tiempo: Approximately 12 months per patient (30 months for treatment arm)
|
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt |
Approximately 12 months per patient (30 months for treatment arm)
|
|
Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Area under the plasma concentration-time curve in one dosing interval (AUCtau)
Periodo de tiempo: Approximately 12 months per patient (30 months for treatment arm)
|
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt |
Approximately 12 months per patient (30 months for treatment arm)
|
|
Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Trough observed concentrations (Ctrough/Ctau)
Periodo de tiempo: Approximately 12 months per patient (30 months for treatment arm)
|
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt |
Approximately 12 months per patient (30 months for treatment arm)
|
|
Phase 1b Combination Therapy: Blood plasma assessment to describe the concentration of rezatapopt and metabolites when rezatapopt is administered orally in combination with pembrolizumab.
Periodo de tiempo: Approximately 12 months per patient (30 months for treatment arm)
|
Blood plasma concentration |
Approximately 12 months per patient (30 months for treatment arm)
|
|
Phase 1b Combination Therapy: Overall Response Rate per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review
Periodo de tiempo: 30 months for study (end of Phase 1b)
|
Evaluation of anti-tumor activity of rezatapopt in combination with pembrolizumab |
30 months for study (end of Phase 1b)
|
|
Phase 1b Combination Therapy: Time to Response per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review
Periodo de tiempo: 30 months for study (end of Phase 1b)
|
Evaluation of anti-tumor activity of rezatapopt in combination with pembrolizumab |
30 months for study (end of Phase 1b)
|
|
Phase 1b Combination Therapy: Duration of Response per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review
Periodo de tiempo: 30 months for study (end of Phase 1b)
|
Evaluation of anti-tumor activity of rezatapopt in combination with pembrolizumab |
30 months for study (end of Phase 1b)
|
|
Phase 1b Combination Therapy: Disease Control Rate per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review
Periodo de tiempo: 30 months for study (end of Phase 1b)
|
Evaluation of anti-tumor activity of rezatapopt in combination with pembrolizumab |
30 months for study (end of Phase 1b)
|
|
Phase 1b Combination Therapy: Overall Survival
Periodo de tiempo: 30 months for study (end of Phase 1b)
|
Evaluation of anti-tumor activity of rezatapopt in combination with pembrolizumab |
30 months for study (end of Phase 1b)
|
|
Phase 1b Combination Therapy: Determine the number and type of adverse events to characterize the safety of rezatapopt
Periodo de tiempo: 30 months for study (end of Phase 1b)
|
Number of participants with treatment related adverse events |
30 months for study (end of Phase 1b)
|
|
Phase 1b Combination Therapy: Progression Free Survival per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review
Periodo de tiempo: 30 months for study (end of Phase 1b)
|
Evaluation of anti-tumor activity of rezatapopt in combination with pembrolizumab |
30 months for study (end of Phase 1b)
|
|
Phase 2 Monotherapy: PK profile of rezatapopt - Time of peak concentration (Tmax)
Periodo de tiempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt |
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
|
Phase 2 Monotherapy: PK profile of rezatapopt - Peak concentration (Cmax)
Periodo de tiempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt |
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
|
Phase 2 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve from time zero to time of last sampling timepoint (AUC0-t)
Periodo de tiempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt |
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
|
Phase 2 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve in one dosing interval (AUCtau)
Periodo de tiempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt |
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
|
Phase 2 Monotherapy: PK profile of rezatapopt - Trough observed concentrations (Ctrough/Ctau)
Periodo de tiempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt |
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
|
Phase 2 Monotherapy: Blood plasma assessment to describe the concentration of rezatapopt and metabolites when rezatapopt is administered orally.
Periodo de tiempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
Blood plasma concentration |
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
|
|
Phase 2 Monotherapy (Dose Expansion): Determine the number and type of adverse events to characterize the safety of rezatapopt
Periodo de tiempo: 34 months for study (end of Phase 2)
|
Number of participants with treatment related adverse events |
34 months for study (end of Phase 2)
|
|
Phase 2 Monotherapy (Dose Expansion): Overall Response Rate across all cohorts per RECIST v1.1 as assessed by Investigator
Periodo de tiempo: 34 months for study (end of Phase 2)
|
Evaluation of anti-tumor activity of rezatapopt as a single agent |
34 months for study (end of Phase 2)
|
|
Phase 2 Monotherapy (Dose Expansion): Overall Response Rate in ovarian cancer cohort per RECIST v1.1 as assessed by Investigator
Periodo de tiempo: 34 months for study (end of Phase 2)
|
Evaluation of anti-tumor activity of rezatapopt as a single agent |
34 months for study (end of Phase 2)
|
|
Phase 2 Monotherapy (Dose Expansion): Time to Response in ovarian cancer cohort per RECIST v1.1 as assessed by Investigator and as assessed by independent review
Periodo de tiempo: 34 months for study (end of Phase 2)
|
Evaluation of anti-tumor activity of rezatapopt as a single agent |
34 months for study (end of Phase 2)
|
|
Phase 2 Monotherapy (Dose Expansion): Time to Response across all cohorts per RECIST v1.1 as assessed by Investigator and as assessed by independent review
Periodo de tiempo: 34 months for study (end of Phase 2)
|
Evaluation of anti-tumor activity of rezatapopt as a single agent |
34 months for study (end of Phase 2)
|
|
Phase 2 Monotherapy (Dose Expansion): Duration of Response in ovarian cancer cohort per RECIST v1.1 as assessed by Investigator and as assessed by independent review
Periodo de tiempo: 34 months for study (end of Phase 2)
|
Evaluation of anti-tumor activity of rezatapopt as a single agent |
34 months for study (end of Phase 2)
|
|
Phase 2 Monotherapy (Dose Expansion): Duration of Response across all cohorts per RECIST v1.1 as assessed by Investigator and as assessed by independent review
Periodo de tiempo: 34 months for study (end of Phase 2)
|
Evaluation of anti-tumor activity of rezatapopt as a single agent |
34 months for study (end of Phase 2)
|
|
Phase 2 Monotherapy (Dose Expansion): Disease Control Rate in ovarian cancer cohort per RECIST v1.1 as assessed by Investigator and as assessed by independent review
Periodo de tiempo: 34 months for study (end of Phase 2)
|
Evaluation of anti-tumor activity of rezatapopt as a single agent |
34 months for study (end of Phase 2)
|
|
Phase 2 Monotherapy (Dose Expansion): Disease Control Rate across all cohorts per RECIST v1.1 as assessed by Investigator and as assessed by independent review
Periodo de tiempo: 34 months for study (end of Phase 2)
|
Evaluation of anti-tumor activity of rezatapopt as a single agent |
34 months for study (end of Phase 2)
|
|
Phase 2 Monotherapy (Dose Expansion): Progression Free Survival in ovarian cancer cohort per RECIST v1.1 as assessed by Investigator and as assessed by independent review
Periodo de tiempo: 34 months for study (end of Phase 2)
|
Evaluation of anti-tumor activity of rezatapopt as a single agent |
34 months for study (end of Phase 2)
|
|
Phase 2 Monotherapy (Dose Expansion): Progression Free Survival across all cohorts per RECIST v1.1 as assessed by Investigator and as assessed by independent review
Periodo de tiempo: 34 months for study (end of Phase 2)
|
Evaluation of anti-tumor activity of rezatapopt as a single agent |
34 months for study (end of Phase 2)
|
|
Phase 2 Monotherapy (Dose Expansion): Overall Survival in ovarian cancer cohort
Periodo de tiempo: 34 months for study (end of Phase 2)
|
Evaluation of anti-tumor activity of rezatapopt as a single agent |
34 months for study (end of Phase 2)
|
|
Phase 2 Monotherapy (Dose Expansion): Overall Survival across all cohorts
Periodo de tiempo: 34 months for study (end of Phase 2)
|
Evaluation of anti-tumor activity of rezatapopt as a single agent |
34 months for study (end of Phase 2)
|
|
Phase 2 Monotherapy (Dose Expansion): Quality of life assessment
Periodo de tiempo: Evaluated at every visit. 34 months for treatment arm (end of Phase 2)
|
Changes from baseline in quality of life as measured by a validated instrument, for participants 18 and older |
Evaluated at every visit. 34 months for treatment arm (end of Phase 2)
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Director de estudio: Marc Fellous, MD, Sr. Vice President, Clinical Development and Medical Affairs
Publicaciones y enlaces útiles
Publicaciones Generales
- Papavassiliou KA, Vassiliou AG, Papavassiliou AG. Rezatapopt: A promising small-molecule "refolder" specific for TP53Y220C mutant tumors. Neoplasia. 2025 Sep;67:101201. doi: 10.1016/j.neo.2025.101201. Epub 2025 Jun 20.
- Schram AM, Fellous M, LeDuke K, Schmid A, Dumbrava EE. PYNNACLE phase II clinical trial protocol: rezatapopt (PC14586) monotherapy in advanced or metastatic solid tumors with a TP53 Y220C mutation. Future Oncol. 2025 Oct;21(24):3159-3166. doi: 10.1080/14796694.2025.2557176. Epub 2025 Sep 11.
- Dumbrava EE, Shapiro GI, Parikh AR, Johnson ML, Tolcher AW, Thompson JA, El-Khoueiry AB, Vandross AL, Kummar S, Shepard DR, LeDuke K, Sheehan L, Alland L, Haque A, Jalota D, Fellous M, Schram AM. Phase 1 Study of Rezatapopt, a p53 Reactivator, in TP53 Y220C-Mutated Tumors. N Engl J Med. 2026 Feb 26;394(9):872-883. doi: 10.1056/NEJMoa2508820.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades urogenitales
- Enfermedades Genitales
- Enfermedades del sistema endocrino
- Procesos Patológicos
- Neoplasias Genitales Masculinas
- Neoplasias urogenitales
- Neoplasias por sitio
- Neoplasias
- Enfermedades Genitales Masculinas
- Enfermedades prostáticas
- Enfermedades urogenitales masculinas
- Enfermedades urogenitales femeninas
- Enfermedades urogenitales femeninas y complicaciones del embarazo
- Enfermedades intestinales
- Enfermedades de las vías respiratorias
- Neoplasias Gastrointestinales
- Neoplasias del Sistema Digestivo
- Enfermedades del Sistema Digestivo
- Enfermedades Gastrointestinales
- Neoplasias Intestinales
- Enfermedades Rectales
- Enfermedades uterinas
- Enfermedades Genitales Femeninas
- Enfermedades pulmonares
- Neoplasias de glándulas endocrinas
- Enfermedades del Tracto Biliar
- Neoplasias de las vías respiratorias
- Neoplasias torácicas
- Enfermedades del Colon
- Procesos Neoplásicos
- Enfermedades Ováricas
- Enfermedades anexiales
- Neoplasias Genitales Femeninas
- Trastornos gonadales
- Enfermedades de la piel
- Enfermedades de los senos
- Carcinoma Broncogénico
- Neoplasias Bronquiales
- Neoplasias Uterinas
- Enfermedades de la vesícula biliar
- Neoplasias del Tracto Biliar
- Condiciones Patológicas, Signos y Síntomas
- Enfermedades de la piel y del tejido conectivo
- Neoplasias prostáticas
- Neoplasias Pulmonares
- Neoplasias colorrectales
- Neoplasias Ováricas
- Neoplasias de mama
- Metástasis de neoplasias
- Carcinoma de pulmón de células no pequeñas
- Neoplasias de Cabeza y Cuello
- Carcinoma de pulmón de células pequeñas
- Neoplasias mamarias triple negativas
- Neoplasias Endometriales
- Neoplasias de vesícula biliar
- pembrolizumab
Otros números de identificación del estudio
- PMV-586-101
- KEYNOTE-D79 (Identificador de registro: Merck, Sharp & Dohme, LLC)
- MK-3475-D79 (Identificador de registro: Merck, Sharp & Dohme, LLC)
Plan de datos de participantes individuales (IPD)
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Información sobre medicamentos y dispositivos, documentos del estudio
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Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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