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Ocena PC14586 u pacjentów z zaawansowanymi guzami litymi z mutacją p53 Y220C

1 października 2026 zaktualizowane przez: PMV Pharmaceuticals, Inc

Otwarte, wieloośrodkowe badanie fazy 1/2 mające na celu ocenę bezpieczeństwa, tolerancji, farmakokinetyki, farmakodynamiki i skuteczności PC14586 u pacjentów z zaawansowanymi guzami litymi z mutacją 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.

Przegląd badań

Status

Rekrutacyjny

Warunki

Interwencja / Leczenie

Szczegółowy opis

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.

Typ studiów

Interwencyjne

Zapisy (Szacowany)

300

Faza

  • Faza 2
  • Faza 1

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Kontakt w sprawie studiów

Lokalizacje studiów

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia
        • Rekrutacyjny
        • Chris O'Brien Lifehouse Hospital
        • Kontakt:
          • Peter Grimison, MD
    • Queensland
      • South Brisbane, Queensland, Australia
        • Rekrutacyjny
        • Mater Cancer Care Centre
        • Kontakt:
          • Catherine Shannon, MD
    • South Australia
      • Bedford Park, South Australia, Australia
        • Rekrutacyjny
        • Flinders Medical Center
        • Kontakt:
          • Shawgi Sukumaran, MD
    • Victoria
      • Clayton, Victoria, Australia
        • Rekrutacyjny
        • Monash Medical Centre
        • Kontakt:
          • Sophia Frentzas, MD
    • Western Australia
      • Nedlands, Western Australia, Australia
        • Rekrutacyjny
        • Linear Clinical Research
        • Kontakt:
          • Michael Millward, MD
  • Francja
      • Lyon, Francja
        • Rekrutacyjny
        • Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer
        • Kontakt:
          • Isabelle Ray-Coquard, MD
      • Nîmes, Francja, 30900
        • Rekrutacyjny
        • CHU de Nîmes
        • Kontakt:
          • Frédéric Fiteni, MD, PhD
      • Vandœuvre-lès-Nancy, Francja, 54519
        • Rekrutacyjny
        • Institute Cancer De Lorraine
        • Kontakt:
          • Aurélien Lambert, MD
    • Bas-Rhin
      • Strasbourg, Bas-Rhin, Francja
        • Rekrutacyjny
        • ICANS - Institut de cancérologie Strasbourg Europe
        • Kontakt:
          • Lauriane Eberst, MD
    • Gironde
      • Bordeaux, Gironde, Francja
        • Rekrutacyjny
        • Institut Bergonie
        • Kontakt:
          • Veronique Debien, MD
    • Haute-Garonne
      • Toulouse, Haute-Garonne, Francja
        • Rekrutacyjny
        • Institut Claudius Regaud
        • Kontakt:
          • Carlos-Alberto Gomez-Roca, MD
    • Loire-Atlantique
      • Saint-Herblain, Loire-Atlantique, Francja
        • Rekrutacyjny
        • EDOG Institut de Cancerologie de l'Ouest
        • Kontakt:
          • Jean-Sebastien Frenel, MD
    • Puy-de-Dôme
      • Clermont-Ferrand, Puy-de-Dôme, Francja
        • Rekrutacyjny
        • Centre Jean Perrin
        • Kontakt:
          • Xavier Durando, MD
    • Val-de-Marne
      • Villejuif, Val-de-Marne, Francja
        • Rekrutacyjny
        • Institut Gustave Roussy
        • Kontakt:
          • Yohann Loriot, MD
  • Hiszpania
      • Barcelona, Hiszpania
        • Rekrutacyjny
        • NEXT Oncology-Hospital Quironsalud Barcelona
        • Kontakt:
          • Elena Garralda, MD
      • Barcelona, Hiszpania
        • Rekrutacyjny
        • Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON
        • Kontakt:
          • Lorena Farinas, MD
      • Madrid, Hiszpania, 28041
        • Rekrutacyjny
        • Hospital Universitario 12 de Octubre
        • Kontakt:
          • Santiago Ponce Aix, MD
      • Rioja, Hiszpania
        • Rekrutacyjny
        • START Rioja
        • Kontakt:
          • Jorge Luis Ramon Patino, MD
      • Valencia, Hiszpania
        • Rekrutacyjny
        • Hospital Clinico Universitario de Valencia
        • Kontakt:
          • José Alejandro Pérez Fidalgo, MD
    • Madrid
      • Madrid, Madrid, Hiszpania
        • Rekrutacyjny
        • START MADRID_Hospital Universitario Fundacion Jimenez Diaz
        • Kontakt:
          • Victor Moreno Garcia, MD
      • Madrid, Madrid, Hiszpania
        • Rekrutacyjny
        • START MADRID_Hospital Universitario HM Sanchinarro - CIOCC
        • Kontakt:
          • Irene Moreno, MD
  • Korea Południowa
      • Seoul, Korea Południowa
        • Rekrutacyjny
        • Samsung Medical Center
        • Kontakt:
          • Chel Hun Choi, MD
      • Seoul, Korea Południowa
        • Rekrutacyjny
        • Asan Medical Center
        • Kontakt:
          • Dae Ho Lee, MD
      • Seoul, Korea Południowa
        • Rekrutacyjny
        • Seoul University Hospital
        • Kontakt:
          • Seock-Ah Im, MD
      • Seoul, Korea Południowa
        • Rekrutacyjny
        • Severance Hospital Yonsei University
        • Kontakt:
          • Jung-Yun Lee, MD
      • Seoul, Korea Południowa
        • Rekrutacyjny
        • National Cancer Center
        • Kontakt:
          • Myong Cheol Lim, MD, PhD
  • Niemcy
    • Baden-Wurttemberg
      • Heidelberg, Baden-Wurttemberg, Niemcy
        • Rekrutacyjny
        • Nationale Centrum für Tumorerkrankungen (NCT) Heidelberg
        • Kontakt:
          • Martin Haag, MD
    • Bavaria
      • Augsburg, Bavaria, Niemcy
        • Rekrutacyjny
        • Universitätsklinikum Augsburg
        • Kontakt:
          • Rainer Claus, MD
    • Free and Hanseatic City of Hamburg
      • Hamburg, Free and Hanseatic City of Hamburg, Niemcy
        • Rekrutacyjny
        • Asklepios Klinik Altona
        • Kontakt:
          • Dirk Arnold, MD
    • Hesse
      • Frankfurt am Main, Hesse, Niemcy
        • Wycofane
        • Universitätsklinikum Frankfurt
    • North Rhine-Westphalia
      • Essen, North Rhine-Westphalia, Niemcy
        • Rekrutacyjny
        • Universitätsklinikum Essen
        • Kontakt:
          • Marcel Wiesweg, MD
  • Singapur
      • Kent Ridge, Singapur
        • Rekrutacyjny
        • National University Hospital
        • Kontakt:
          • David Shao Peng Tan, MD
      • Singapore, Singapur, 168582
        • Rekrutacyjny
        • National Cancer Center of Singapore
        • Kontakt:
          • Tira Tan, MD
  • Stany Zjednoczone
    • California
      • Irvine, California, Stany Zjednoczone, 92868
        • Wycofane
        • University of California Irvine Chao Family Comprehensive Cancer Center
      • La Jolla, California, Stany Zjednoczone, 92093
        • Rekrutacyjny
        • University of San Diego Moores Cancer Center
        • Kontakt:
          • Shumei Kato, MD
      • Los Angeles, California, Stany Zjednoczone, 90033
        • Rekrutacyjny
        • USC Norris Comprehensive Cancer Center
        • Kontakt:
          • Anthony El-Khoueiry, MD
      • Los Angeles, California, Stany Zjednoczone, 90024
        • Rekrutacyjny
        • UCLA Jonsson Comprehensive Cancer Center
        • Kontakt:
          • Gottfried Konecny, MD
    • Colorado
      • Denver, Colorado, Stany Zjednoczone, 80218
        • Rekrutacyjny
        • Rocky Mountain Cancer Center
        • Kontakt:
          • Allen Cohn, MD
    • Connecticut
      • New Haven, Connecticut, Stany Zjednoczone, 06519
        • Rekrutacyjny
        • Yale Cancer Center
        • Kontakt:
          • Patricia LoRusso, MD
    • Delaware
      • Newark, Delaware, Stany Zjednoczone, 19713
        • Rekrutacyjny
        • Medical Oncology Hematology Consultants
        • Kontakt:
          • Jamal Misleh, MD
    • Florida
      • Miami, Florida, Stany Zjednoczone, 33136
        • Rekrutacyjny
        • University of Miami - Sylvester Comprehensive Cancer Center
        • Kontakt:
          • Gilberto de Lima Lopes Jr., MD
      • Orlando, Florida, Stany Zjednoczone, 32803
        • Rekrutacyjny
        • Advent Health
        • Kontakt:
          • Robert Holloway, MD
      • Port Charlotte, Florida, Stany Zjednoczone, 33980
        • Rekrutacyjny
        • Florida Cancer Specialists South
        • Kontakt:
          • Ivor Percent, MD
    • Massachusetts
      • Boston, Massachusetts, Stany Zjednoczone, 02114
        • Rekrutacyjny
        • Massachusetts General Hospital
        • Kontakt:
          • Aparna Parikh, MD
      • Boston, Massachusetts, Stany Zjednoczone, 02215
        • Rekrutacyjny
        • Dana Farber Cancer Institute
        • Kontakt:
          • Geoffrey Shapiro, MD, PhD
    • Michigan
      • Detroit, Michigan, Stany Zjednoczone, 48201
        • Zakończony
        • Karmanos Cancer Institute
    • New York
      • New York, New York, Stany Zjednoczone, 10065
        • Rekrutacyjny
        • Memorial Sloan Kettering
        • Kontakt:
          • Alison Schram, MD
      • New York, New York, Stany Zjednoczone, 10032
        • Jeszcze nie rekrutacja
        • Columbia University Medical Center
        • Kontakt:
          • June Hou, MD
    • North Carolina
      • Durham, North Carolina, Stany Zjednoczone, 27705
        • Rekrutacyjny
        • Duke University
        • Kontakt:
          • Niharika Mettu, MD, PhD
    • Ohio
      • Cleveland, Ohio, Stany Zjednoczone, 44195
        • Rekrutacyjny
        • The Cleveland Clinic Taussig Cancer Center
        • Kontakt:
          • Dale Shepard, MD
    • Oklahoma
      • Oklahoma City, Oklahoma, Stany Zjednoczone, 73104
        • Rekrutacyjny
        • University of Oklahoma
        • Kontakt:
          • Debra Richardson, MD
    • Oregon
      • Portland, Oregon, Stany Zjednoczone, 97210
        • Rekrutacyjny
        • Oregon Health & Science University (OHSU)
        • Kontakt:
          • Shivaani Kummar, MD
    • Pennsylvania
      • Philadelphia, Pennsylvania, Stany Zjednoczone, 19104
        • Rekrutacyjny
        • Abramson Cancer Center of the University of Pennsylvania
        • Kontakt:
          • Lainie Martin, MD
      • Pittsburgh, Pennsylvania, Stany Zjednoczone, 15213
        • Rekrutacyjny
        • University of Pittsburgh Medical Center
        • Kontakt:
          • Sarah Taylor, MD, PhD
      • York, Pennsylvania, Stany Zjednoczone, 17403
        • Rekrutacyjny
        • WellSpan York Cancer Center
        • Kontakt:
          • Ikechukwu Akunyili, MD
    • South Carolina
      • Charleston, South Carolina, Stany Zjednoczone, 29425
        • Zakończony
        • Medical University of South Carolina
    • Tennessee
      • Nashville, Tennessee, Stany Zjednoczone, 37203
        • Rekrutacyjny
        • Sarah Cannon Research Institute
        • Kontakt:
          • Melissa Johnson, MD
    • Texas
      • Austin, Texas, Stany Zjednoczone, 78705
        • Rekrutacyjny
        • New Experimental Therapeutics - NEXT Oncology
        • Kontakt:
          • David Sommerhalder, MD
      • Bedford, Texas, Stany Zjednoczone, 76022
        • Rekrutacyjny
        • Texas Oncology
        • Kontakt:
          • Terrence Wong, MD
      • Dallas, Texas, Stany Zjednoczone, 75390
        • Rekrutacyjny
        • UT Southwest Simmons Cancer Center
        • Kontakt:
          • David Miller, MD
      • Houston, Texas, Stany Zjednoczone, 77030
        • Rekrutacyjny
        • The University of Texas MD Anderson Cancer Center
        • Kontakt:
          • Ecaterina Dumbrava, MD
      • San Antonio, Texas, Stany Zjednoczone, 78229
        • Rekrutacyjny
        • New Experimental Therapeutics of San Antonio - NEXT Oncology
        • Kontakt:
          • David Sommerhalder, MD
    • Virginia
      • Fairfax, Virginia, Stany Zjednoczone, 22031
        • Rekrutacyjny
        • Virginia Cancer Specialists
        • Kontakt:
          • Alexander Spira, MD
    • Washington
      • Seattle, Washington, Stany Zjednoczone, 98109
        • Rekrutacyjny
        • University of Washington, Fred Hutchinson Cancer Center
        • Kontakt:
          • Andrew Coveler, MD
    • Wisconsin
      • Madison, Wisconsin, Stany Zjednoczone, 53705
        • Rekrutacyjny
        • University of Wisconsin Carbone Cancer Center
        • Kontakt:
          • Nataliya Uboha, MD, PhD
  • Włochy
      • Milan, Włochy
        • Rekrutacyjny
        • Humanitas San Pio X
        • Kontakt:
          • Domenica Lorusso, MD
      • Naples, Włochy, 80131
        • Rekrutacyjny
        • IRCCS - lstituto Nazionale Tumori - Fondazione G. Pascale
        • Kontakt:
          • Anna Passarelli, MD
    • Lazio
      • Rome, Lazio, Włochy
        • Rekrutacyjny
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
        • Kontakt:
          • Anna Fagotti, MD
      • Rome, Lazio, Włochy
        • Rekrutacyjny
        • Istituti Fisioterapici Ospitalieri - Istituto Nazionale Tumori Regina Elena
        • Kontakt:
          • Lorenza Landi, MD
    • Lombardy
      • Milan, Lombardy, Włochy
        • Rekrutacyjny
        • ASST Grande Ospedale Metropolitano Niguarda
        • Kontakt:
          • Salvatore Siena, MD
      • Milan, Lombardy, Włochy
        • Rekrutacyjny
        • Fondazione IRCCS Istituto Nazionale Dei Tumori
        • Kontakt:
          • Massimo Di Nicola, MD
      • Milan, Lombardy, Włochy
        • Rekrutacyjny
        • Istituto Europeo Di Oncologia
        • Kontakt:
          • Giuseppe Curigliano, MD
      • Rozzano, Lombardy, Włochy
        • Rekrutacyjny
        • Istituto Clinico Humanitas
        • Kontakt:
          • Armando Santoro, MD
    • Torino
      • Candiolo, Torino, Włochy
        • Rekrutacyjny
        • Fondazione del Piemonte per l'Oncologia (IRCCS)
        • Kontakt:
          • Chiara Lazzari, MD
  • Zjednoczone Królestwo
    • Middlesex
      • London, Middlesex, Zjednoczone Królestwo
        • Rekrutacyjny
        • Sarah Cannon Research Institute UK
        • Kontakt:
          • Elisa Fontana, MD, PhD
    • Tyne and Wear
      • Newcastle upon Tyne, Tyne and Wear, Zjednoczone Królestwo
        • Rekrutacyjny
        • Freeman Hospital
        • Kontakt:
          • Alastair Greystoke, MB ChB PhD

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

12 lat i starsze (Dziecko, Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

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 studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Nielosowe
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: 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).
Lek: rezatapopt

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

Inne nazwy:
  • PC14586
Eksperymentalny: 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.
Lek: rezatapopt

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

Inne nazwy:
  • PC14586
Lek: pembrolizumab

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

Inne nazwy:
  • MK-3475
  • KEYTRUDA®
  • KEYNOTE-D79
  • MK-3475-D79
Eksperymentalny: 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.
Lek: rezatapopt

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

Inne nazwy:
  • PC14586
Lek: pembrolizumab

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

Inne nazwy:
  • MK-3475
  • KEYTRUDA®
  • KEYNOTE-D79
  • MK-3475-D79
Eksperymentalny: 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.
Lek: rezatapopt

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

Inne nazwy:
  • PC14586
Lek: pembrolizumab

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

Inne nazwy:
  • MK-3475
  • KEYTRUDA®
  • KEYNOTE-D79
  • MK-3475-D79
Eksperymentalny: 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.
Lek: rezatapopt

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

Inne nazwy:
  • PC14586
Eksperymentalny: 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.
Lek: rezatapopt

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

Inne nazwy:
  • PC14586
Eksperymentalny: 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.
Lek: rezatapopt

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

Inne nazwy:
  • PC14586
Eksperymentalny: 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.
Lek: rezatapopt

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

Inne nazwy:
  • PC14586
Eksperymentalny: 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.
Lek: rezatapopt

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

Inne nazwy:
  • PC14586

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt
Ramy czasowe: 40 months

Number of participants with treatment related adverse events
40 months
Phase 1 Monotherapy (Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D)
Ramy czasowe: 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)
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Phase 1 Monotherapy: PK profile of rezatapopt - Peak concentration (Cmax)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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.
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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.
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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.
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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)

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

PMV Pharmaceuticals, Inc

Współpracownicy

Merck Sharp & Dohme LLC

Śledczy

  • Dyrektor Studium: Marc Fellous, MD, Sr. Vice President, Clinical Development and Medical Affairs

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Publikacje ogólne

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Rzeczywisty)

29 października 2020

Zakończenie podstawowe (Szacowany)

15 grudnia 2026

Ukończenie studiów (Szacowany)

31 grudnia 2027

Daty rejestracji na studia

Pierwszy przesłany

1 października 2020

Pierwszy przesłany, który spełnia kryteria kontroli jakości

7 października 2020

Pierwszy wysłany (Rzeczywisty)

14 października 2020

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

2 października 2026

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

1 października 2026

Ostatnia weryfikacja

1 października 2026

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • PMV-586-101
  • KEYNOTE-D79 (Identyfikator rejestru: Merck, Sharp & Dohme, LLC)
  • MK-3475-D79 (Identyfikator rejestru: Merck, Sharp & Dohme, LLC)

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

NIE

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Tak

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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