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Оценка PC14586 у пациентов с прогрессирующими солидными опухолями, несущими мутацию p53 Y220C

1 октября 2026 г. обновлено: PMV Pharmaceuticals, Inc

Открытое многоцентровое исследование фазы 1/2 для оценки безопасности, переносимости, фармакокинетики, фармакодинамики и эффективности PC14586 у пациентов с запущенными солидными опухолями, содержащими мутацию 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.

Обзор исследования

Статус

Рекрутинг

Условия

Вмешательство/лечение

Подробное описание

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.

Тип исследования

Интервенционный

Регистрация (Оцененный)

300

Фаза

  • Фаза 2
  • Фаза 1

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Контакты исследования

  • Имя: PMV Pharma Clinical Study Information Center
  • Номер телефона: (609) 235-4038
  • Электронная почта: clinicaltrials@pmvpharma.com

Места учебы

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

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

12 лет и старше (Ребенок, Взрослый, Пожилой взрослый)

Принимает здоровых добровольцев

Нет

Полы, имеющие право на обучение

Все

Описание

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

Учебный план

В этом разделе представлена ​​подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

  • Основная цель: Уход
  • Распределение: Нерандомизированный
  • Интервенционная модель: Параллельное назначение
  • Маскировка: Нет (открытая этикетка)

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Экспериментальный: 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).
Лекарство: rezatapopt

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

Другие имена:
  • PC14586
Экспериментальный: 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.
Лекарство: rezatapopt

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

Другие имена:
  • PC14586
Лекарство: pembrolizumab

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

Другие имена:
  • МК-3475
  • КЕЙТРУДА®
  • KEYNOTE-D79
  • МК-3475-Д79
Экспериментальный: 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.
Лекарство: rezatapopt

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

Другие имена:
  • PC14586
Лекарство: pembrolizumab

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

Другие имена:
  • МК-3475
  • КЕЙТРУДА®
  • KEYNOTE-D79
  • МК-3475-Д79
Экспериментальный: 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.
Лекарство: rezatapopt

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

Другие имена:
  • PC14586
Лекарство: pembrolizumab

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

Другие имена:
  • МК-3475
  • КЕЙТРУДА®
  • KEYNOTE-D79
  • МК-3475-Д79
Экспериментальный: 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.
Лекарство: rezatapopt

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

Другие имена:
  • PC14586
Экспериментальный: 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.
Лекарство: rezatapopt

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

Другие имена:
  • PC14586
Экспериментальный: 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.
Лекарство: rezatapopt

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

Другие имена:
  • PC14586
Экспериментальный: 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.
Лекарство: rezatapopt

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

Другие имена:
  • PC14586
Экспериментальный: 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.
Лекарство: rezatapopt

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

Другие имена:
  • PC14586

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt
Временное ограничение: 40 months

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

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Phase 1 Monotherapy: PK profile of rezatapopt - Peak concentration (Cmax)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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.
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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.
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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.
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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)

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

PMV Pharmaceuticals, Inc

Соавторы

Merck Sharp & Dohme LLC

Следователи

  • Директор по исследованиям: Marc Fellous, MD, Sr. Vice President, Clinical Development and Medical Affairs

Публикации и полезные ссылки

Лицо, ответственное за внесение сведений об исследовании, добровольно предоставляет эти публикации. Это может быть что угодно, связанное с исследованием.

Общие публикации

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования (Действительный)

29 октября 2020 г.

Первичное завершение (Оцененный)

15 декабря 2026 г.

Завершение исследования (Оцененный)

31 декабря 2027 г.

Даты регистрации исследования

Первый отправленный

1 октября 2020 г.

Впервые представлено, что соответствует критериям контроля качества

7 октября 2020 г.

Первый опубликованный (Действительный)

14 октября 2020 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)

2 октября 2026 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

1 октября 2026 г.

Последняя проверка

1 октября 2026 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

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

Планирование данных отдельных участников (IPD)

Планируете делиться данными об отдельных участниках (IPD)?

НЕТ

Информация о лекарствах и устройствах, исследовательские документы

Изучает лекарственный продукт, регулируемый FDA США.

Да

Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.

Нет

Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .

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