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PC14586:n arviointi potilailla, joilla on edennyt kiinteitä kasvaimia, joissa on p53 Y220C -mutaatio

torstai 1. lokakuuta 2026 päivittänyt: PMV Pharmaceuticals, Inc

Vaiheen 1/2 avoin monikeskustutkimus PC14586:n turvallisuuden, siedettävyyden, farmakokinetiikka, farmakodynamiikka ja tehon arvioimiseksi potilailla, joilla on edennyt kiinteitä kasvaimia ja joissa on p53 Y220C -mutaatio (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.

Tutkimuksen yleiskatsaus

Tila

Rekrytointi

Ehdot

Interventio / Hoito

Yksityiskohtainen kuvaus

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.

Opintotyyppi

Interventio

Ilmoittautuminen (Arvioitu)

300

Vaihe

  • Vaihe 2
  • Vaihe 1

Yhteystiedot ja paikat

Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.

Opiskeluyhteys

Opiskelupaikat

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

Osallistumiskriteerit

Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.

Kelpoisuusvaatimukset

Opintokelpoiset iät

12 vuotta ja vanhemmat (Lapsi, Aikuinen, Vanhempi Aikuinen)

Hyväksyy terveitä vapaaehtoisia

Ei

Sukupuolet, jotka voivat opiskella

Kaikki

Kuvaus

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

Opintosuunnitelma

Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.

Miten tutkimus on suunniteltu?

Suunnittelun yksityiskohdat

  • Ensisijainen käyttötarkoitus: Hoito
  • Jako: Ei satunnaistettu
  • Inventiomalli: Rinnakkaistehtävä
  • Naamiointi: Ei mitään (avoin tarra)

Aseet ja interventiot

Osallistujaryhmä / Arm
Interventio / Hoito
Kokeellinen: 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).
Lääke: rezatapopt

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

Muut nimet:
  • PC14586
Kokeellinen: 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.
Lääke: rezatapopt

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

Muut nimet:
  • PC14586
Lääke: pembrolizumab

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

Muut nimet:
  • MK-3475
  • KEYTRUDA®
  • KEYNOTE-D79
  • MK-3475-D79
Kokeellinen: 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.
Lääke: rezatapopt

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

Muut nimet:
  • PC14586
Lääke: pembrolizumab

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

Muut nimet:
  • MK-3475
  • KEYTRUDA®
  • KEYNOTE-D79
  • MK-3475-D79
Kokeellinen: 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.
Lääke: rezatapopt

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

Muut nimet:
  • PC14586
Lääke: pembrolizumab

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

Muut nimet:
  • MK-3475
  • KEYTRUDA®
  • KEYNOTE-D79
  • MK-3475-D79
Kokeellinen: 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.
Lääke: rezatapopt

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

Muut nimet:
  • PC14586
Kokeellinen: 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.
Lääke: rezatapopt

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

Muut nimet:
  • PC14586
Kokeellinen: 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.
Lääke: rezatapopt

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

Muut nimet:
  • PC14586
Kokeellinen: 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.
Lääke: rezatapopt

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

Muut nimet:
  • PC14586
Kokeellinen: 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.
Lääke: rezatapopt

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

Muut nimet:
  • PC14586

Mitä tutkimuksessa mitataan?

Ensisijaiset tulostoimenpiteet

Tulosmittaus
Toimenpiteen kuvaus
Aikaikkuna
Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt
Aikaikkuna: 40 months

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

Toissijaiset tulostoimenpiteet

Tulosmittaus
Toimenpiteen kuvaus
Aikaikkuna
Phase 1 Monotherapy: PK profile of rezatapopt - Peak concentration (Cmax)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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.
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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.
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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.
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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)

Yhteistyökumppanit ja tutkijat

Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.

Sponsori

PMV Pharmaceuticals, Inc

Yhteistyökumppanit

Merck Sharp & Dohme LLC

Tutkijat

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

Julkaisuja ja hyödyllisiä linkkejä

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Opi tärkeimmät päivämäärät

Opiskelun aloitus (Todellinen)

Torstai 29. lokakuuta 2020

Ensisijainen valmistuminen (Arvioitu)

Tiistai 15. joulukuuta 2026

Opintojen valmistuminen (Arvioitu)

Perjantai 31. joulukuuta 2027

Opintoihin ilmoittautumispäivät

Ensimmäinen lähetetty

Torstai 1. lokakuuta 2020

Ensimmäinen toimitettu, joka täytti QC-kriteerit

Keskiviikko 7. lokakuuta 2020

Ensimmäinen Lähetetty (Todellinen)

Keskiviikko 14. lokakuuta 2020

Tutkimustietojen päivitykset

Viimeisin päivitys julkaistu (Todellinen)

Perjantai 2. lokakuuta 2026

Viimeisin lähetetty päivitys, joka täytti QC-kriteerit

Torstai 1. lokakuuta 2026

Viimeksi vahvistettu

Torstai 1. lokakuuta 2026

Lisää tietoa

Tähän tutkimukseen liittyvät termit

Avainsanat

Muita asiaankuuluvia MeSH-ehtoja

Muut tutkimustunnusnumerot

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

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