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L'évaluation de PC14586 chez les patients atteints de tumeurs solides avancées hébergeant une mutation p53 Y220C

1 octobre 2026 mis à jour par: PMV Pharmaceuticals, Inc

Une étude multicentrique ouverte de phase 1/2 pour évaluer l'innocuité, la tolérance, la pharmacocinétique, la pharmacodynamique et l'efficacité du PC14586 chez les patients atteints de tumeurs solides avancées hébergeant une mutation 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.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Estimé)

300

Phase

  • Phase 2
  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

12 ans et plus (Enfant, Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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 d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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).
Médicament: rezatapopt

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

Autres noms:
  • PC14586
Expérimental: 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.
Médicament: rezatapopt

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

Autres noms:
  • PC14586
Médicament: pembrolizumab

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

Autres noms:
  • MK-3475
  • KEYTRUDA®
  • KEYNOTE-D79
  • MK-3475-D79
Expérimental: 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.
Médicament: rezatapopt

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

Autres noms:
  • PC14586
Médicament: pembrolizumab

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

Autres noms:
  • MK-3475
  • KEYTRUDA®
  • KEYNOTE-D79
  • MK-3475-D79
Expérimental: 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.
Médicament: rezatapopt

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

Autres noms:
  • PC14586
Médicament: pembrolizumab

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

Autres noms:
  • MK-3475
  • KEYTRUDA®
  • KEYNOTE-D79
  • MK-3475-D79
Expérimental: 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.
Médicament: rezatapopt

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

Autres noms:
  • PC14586
Expérimental: 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.
Médicament: rezatapopt

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

Autres noms:
  • PC14586
Expérimental: 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.
Médicament: rezatapopt

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

Autres noms:
  • PC14586
Expérimental: 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.
Médicament: rezatapopt

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

Autres noms:
  • PC14586
Expérimental: 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.
Médicament: rezatapopt

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

Autres noms:
  • PC14586

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt
Délai: 40 months

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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Phase 1 Monotherapy: PK profile of rezatapopt - Peak concentration (Cmax)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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.
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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.
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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.
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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)

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

PMV Pharmaceuticals, Inc

Collaborateurs

Merck Sharp & Dohme LLC

Les enquêteurs

  • Directeur d'études: Marc Fellous, MD, Sr. Vice President, Clinical Development and Medical Affairs

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

29 octobre 2020

Achèvement primaire (Estimé)

15 décembre 2026

Achèvement de l'étude (Estimé)

31 décembre 2027

Dates d'inscription aux études

Première soumission

1 octobre 2020

Première soumission répondant aux critères de contrôle qualité

7 octobre 2020

Première publication (Réel)

14 octobre 2020

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

2 octobre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

1 octobre 2026

Dernière vérification

1 octobre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • PMV-586-101
  • KEYNOTE-D79 (Identificateur de registre: Merck, Sharp & Dohme, LLC)
  • MK-3475-D79 (Identificateur de registre: Merck, Sharp & Dohme, LLC)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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