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Advanced Solid TumorPhase 1/2NCT04585750

The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)

A Phase 1/2 study testing rezatapopt and pembrolizumab in people with Advanced Solid Tumor and Advanced Malignant Neoplasm, run by PMV Pharmaceuticals, Inc at 76 sites in 9 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
rezatapopt and pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
300 participants
Where
76 sitesin 9 countries
Study dates
29 Oct 2020to 31 Dec 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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)
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  • Additional Criteria for Inclusion in Phase 1b (rezatapopt) + pembrolizumab combination)
  • Anti-PD-1/PD-L1 naive or must have progressed on treatment
  • Measurable disease

Who cannot join

  • 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
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  • 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

Trial locations and contacts

76 sites in 9 countries. Contact the study team or a site near you to ask about taking part.

PMV Pharma Clinical Study Information Center contact

(609) 235-4038

clinicaltrials@pmvpharma.com

76 sites in 9 countries

United States32 sites, 29 recruiting

  • New Experimental Therapeutics - NEXT Oncology

    Austin, Texas, 78705

    David Sommerhalder, MD

    Recruiting

  • Texas Oncology

    Bedford, Texas, 76022

    Terrence Wong, MD

    Recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Aparna Parikh, MD

    Recruiting

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

    Geoffrey Shapiro, MD, PhD

    Recruiting

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

    Terminated

  • The Cleveland Clinic Taussig Cancer Center

    Cleveland, Ohio, 44195

    Dale Shepard, MD

    Recruiting

  • UT Southwest Simmons Cancer Center

    Dallas, Texas, 75390

    David Miller, MD

    Recruiting

  • Rocky Mountain Cancer Center

    Denver, Colorado, 80218

    Allen Cohn, MD

    Recruiting

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

    Completed

  • Duke University

    Durham, North Carolina, 27705

    Niharika Mettu, MD, PhD

    Recruiting

  • Virginia Cancer Specialists

    Fairfax, Virginia, 22031

    Alexander Spira, MD

    Recruiting

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

    Ecaterina Dumbrava, MD

    Recruiting

  • University of California Irvine Chao Family Comprehensive Cancer Center

    Irvine, California, 92868

    Withdrawn

  • University of San Diego Moores Cancer Center

    La Jolla, California, 92093

    Shumei Kato, MD

    Recruiting

  • UCLA Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90024

    Gottfried Konecny, MD

    Recruiting

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

    Anthony El-Khoueiry, MD

    Recruiting

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53705

    Nataliya Uboha, MD, PhD

    Recruiting

  • University of Miami - Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

    Gilberto de Lima Lopes Jr., MD

    Recruiting

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

    Melissa Johnson, MD

    Recruiting

  • Yale Cancer Center

    New Haven, Connecticut, 06519

    Patricia LoRusso, MD

    Recruiting

  • Columbia University Medical Center

    New York, New York, 10032

    June Hou, MD

    Not yet recruiting

  • Memorial Sloan Kettering

    New York, New York, 10065

    Alison Schram, MD

    Recruiting

  • Medical Oncology Hematology Consultants

    Newark, Delaware, 19713

    Jamal Misleh, MD

    Recruiting

  • University of Oklahoma

    Oklahoma City, Oklahoma, 73104

    Debra Richardson, MD

    Recruiting

  • Advent Health

    Orlando, Florida, 32803

    Robert Holloway, MD

    Recruiting

  • Abramson Cancer Center of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

    Lainie Martin, MD

    Recruiting

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

    Sarah Taylor, MD, PhD

    Recruiting

  • Florida Cancer Specialists South

    Port Charlotte, Florida, 33980

    Ivor Percent, MD

    Recruiting

  • Oregon Health & Science University (OHSU)

    Portland, Oregon, 97210

    Shivaani Kummar, MD

    Recruiting

  • New Experimental Therapeutics of San Antonio - NEXT Oncology

    San Antonio, Texas, 78229

    David Sommerhalder, MD

    Recruiting

  • University of Washington, Fred Hutchinson Cancer Center

    Seattle, Washington, 98109

    Andrew Coveler, MD

    Recruiting

  • WellSpan York Cancer Center

    York, Pennsylvania, 17403

    Ikechukwu Akunyili, MD

    Recruiting

Other trials in United States

France9 sites, 9 recruiting

  • Institut Bergonie

    Bordeaux, Gironde

    Veronique Debien, MD

    Recruiting

  • Centre Jean Perrin

    Clermont-Ferrand, Puy-de-Dôme

    Xavier Durando, MD

    Recruiting

  • Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer

    Lyon

    Isabelle Ray-Coquard, MD

    Recruiting

  • CHU de Nîmes

    Nîmes, 30900

    Frédéric Fiteni, MD, PhD

    Recruiting

  • EDOG Institut de Cancerologie de l'Ouest

    Saint-Herblain, Loire-Atlantique

    Jean-Sebastien Frenel, MD

    Recruiting

  • ICANS - Institut de cancérologie Strasbourg Europe

    Strasbourg, Bas-Rhin

    Lauriane Eberst, MD

    Recruiting

  • Institut Claudius Regaud

    Toulouse, Haute-Garonne

    Carlos-Alberto Gomez-Roca, MD

    Recruiting

  • Institute Cancer De Lorraine

    Vandœuvre-lès-Nancy, 54519

    Aurélien Lambert, MD

    Recruiting

  • Institut Gustave Roussy

    Villejuif, Val-de-Marne

    Yohann Loriot, MD

    Recruiting

Other trials in France

Italy9 sites, 9 recruiting

  • Fondazione del Piemonte per l'Oncologia (IRCCS)

    Candiolo, Torino

    Chiara Lazzari, MD

    Recruiting

  • ASST Grande Ospedale Metropolitano Niguarda

    Milan, Lombardy

    Salvatore Siena, MD

    Recruiting

  • Fondazione IRCCS Istituto Nazionale Dei Tumori

    Milan, Lombardy

    Massimo Di Nicola, MD

    Recruiting

  • Istituto Europeo Di Oncologia

    Milan, Lombardy

    Giuseppe Curigliano, MD

    Recruiting

  • Humanitas San Pio X

    Milan

    Domenica Lorusso, MD

    Recruiting

  • IRCCS - lstituto Nazionale Tumori - Fondazione G. Pascale

    Naples, 80131

    Anna Passarelli, MD

    Recruiting

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

    Rome, Lazio

    Anna Fagotti, MD

    Recruiting

  • Istituti Fisioterapici Ospitalieri - Istituto Nazionale Tumori Regina Elena

    Rome, Lazio

    Lorenza Landi, MD

    Recruiting

  • Istituto Clinico Humanitas

    Rozzano, Lombardy

    Armando Santoro, MD

    Recruiting

Other trials in Italy

Spain7 sites, 7 recruiting

  • Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON

    Barcelona

    Lorena Farinas, MD

    Recruiting

  • NEXT Oncology-Hospital Quironsalud Barcelona

    Barcelona

    Elena Garralda, MD

    Recruiting

  • START MADRID_Hospital Universitario Fundacion Jimenez Diaz

    Madrid, Madrid

    Victor Moreno Garcia, MD

    Recruiting

  • START MADRID_Hospital Universitario HM Sanchinarro - CIOCC

    Madrid, Madrid

    Irene Moreno, MD

    Recruiting

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

    Santiago Ponce Aix, MD

    Recruiting

  • START Rioja

    Rioja

    Jorge Luis Ramon Patino, MD

    Recruiting

  • Hospital Clinico Universitario de Valencia

    Valencia

    José Alejandro Pérez Fidalgo, MD

    Recruiting

Other trials in Spain

Australia5 sites, 5 recruiting

  • Flinders Medical Center

    Bedford Park, South Australia

    Shawgi Sukumaran, MD

    Recruiting

  • Chris O'Brien Lifehouse Hospital

    Camperdown, New South Wales

    Peter Grimison, MD

    Recruiting

  • Monash Medical Centre

    Clayton, Victoria

    Sophia Frentzas, MD

    Recruiting

  • Linear Clinical Research

    Nedlands, Western Australia

    Michael Millward, MD

    Recruiting

  • Mater Cancer Care Centre

    South Brisbane, Queensland

    Catherine Shannon, MD

    Recruiting

Other trials in Australia

Germany5 sites, 4 recruiting

  • Universitätsklinikum Augsburg

    Augsburg, Bavaria

    Rainer Claus, MD

    Recruiting

  • Universitätsklinikum Essen

    Essen, North Rhine-Westphalia

    Marcel Wiesweg, MD

    Recruiting

  • Universitätsklinikum Frankfurt

    Frankfurt am Main, Hesse

    Withdrawn

  • Asklepios Klinik Altona

    Hamburg, Free and Hanseatic City of Hamburg

    Dirk Arnold, MD

    Recruiting

  • Nationale Centrum für Tumorerkrankungen (NCT) Heidelberg

    Heidelberg, Baden-Wurttemberg

    Martin Haag, MD

    Recruiting

Other trials in Germany

South Korea5 sites, 5 recruiting

  • Asan Medical Center

    Seoul

    Dae Ho Lee, MD

    Recruiting

  • National Cancer Center

    Seoul

    Myong Cheol Lim, MD, PhD

    Recruiting

  • Samsung Medical Center

    Seoul

    Chel Hun Choi, MD

    Recruiting

  • Seoul University Hospital

    Seoul

    Seock-Ah Im, MD

    Recruiting

  • Severance Hospital Yonsei University

    Seoul

    Jung-Yun Lee, MD

    Recruiting

Other trials in South Korea

Singapore2 sites, 2 recruiting

  • National University Hospital

    Kent Ridge

    David Shao Peng Tan, MD

    Recruiting

  • National Cancer Center of Singapore

    Singapore, 168582

    Tira Tan, MD

    Recruiting

Other trials in Singapore

United Kingdom2 sites, 2 recruiting

  • Sarah Cannon Research Institute UK

    London, Middlesex

    Elisa Fontana, MD, PhD

    Recruiting

  • Freeman Hospital

    Newcastle upon Tyne, Tyne and Wear

    Alastair Greystoke, MB ChB PhD

    Recruiting

Other trials in United Kingdom

About this study

Official title: A Phase 1/2 Open-label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of PC14586 in Patients With Locally Advanced or Metastatic Solid Tumors Harboring a TP53 Y220C Mutation (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.

Read the detailed description

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.

Being tested
rezatapopt, pembrolizumab
Keywords
PC14586, p53, Y220C, Phase 1, Phase 1/2, PMV, PMV Pharma, p53 mutation, TP53, TP53 mutation, p53 mutant, p53 reactivator, pembrolizumab, Keytruda, combination, PD-1, PD-L1, anti-PD-1, Merck, MSD
Medical subject headings
Neoplasm Metastasis, Lung Neoplasms, Ovarian Neoplasms, Endometrial Neoplasms, Prostatic Neoplasms, Colorectal Neoplasms, Breast Neoplasms, Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rezatapoptDrug

    Also called PC14586

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

  • pembrolizumabDrug

    Also called KEYTRUDA®, MK-3475, KEYNOTE-D79, MK-3475-D79

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

Study groups in NCT04585750
Study groupRoleWhat they receive
Phase 1 Monotherapy Dose EscalationExperimentalMultiple 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).
Receives: Drug: rezatapopt
Phase 1b Combination Therapy Dose Escalation, Part 1ExperimentalMultiple 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.
Receives: Drug: rezatapopt; Drug: pembrolizumab
Phase 1b Combination Therapy Dose Expansion, PD(L)-1 naive patientsExperimentalAdditional (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.
Receives: Drug: rezatapopt; Drug: pembrolizumab
Phase 1b Combination Therapy Dose Expansion, PD(L)-1 relapsed/refractory patientsExperimentalAdditional (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.
Receives: Drug: rezatapopt; Drug: pembrolizumab
Phase 2 Monotherapy Dose Expansion, Ovarian Cancer CohortExperimentalAdditional (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.
Receives: Drug: rezatapopt
Phase 2 Monotherapy Dose Expansion, Lung Cancer CohortExperimentalAdditional (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.
Receives: Drug: rezatapopt
Phase 2 Monotherapy Dose Expansion, Breast Cancer CohortExperimentalAdditional (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.
Receives: Drug: rezatapopt
Phase 2 Monotherapy Dose Expansion, Endometrial Cancer CohortExperimentalAdditional (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.
Receives: Drug: rezatapopt
Phase 2 Monotherapy Dose Expansion, Other Solid Tumors CohortExperimentalAdditional (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.
Receives: Drug: rezatapopt

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt

    Number of participants with treatment related adverse events

    Measured: 40 months

  2. Phase 1 Monotherapy (Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D)

    RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data

    Measured: 30 months

  3. Phase 1 Monotherapy (Dose Escalation): Establish the maximum tolerated dose (MTD) (Phase 1)

    Incidence of dose limiting toxicities (DLTs) during the first 28 days of treatment with rezatapopt

    Measured: The first 28 days of treatment (Cycle 1) per patient

  4. 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

    Number of participants with treatment related adverse events

    Measured: 18 months for treatment arm

  5. Phase 1b Combination Therapy (Part 1: Dose Escalation): Establish the maximum tolerated dose (MTD) of rezatapopt when administered in combination with pembrolizumab

    Incidence of dose limiting toxicities (DLTs) during the first 28 days of treatment with rezatapopt

    Measured: The first 28 days of combination treatment arm (starting on Day -7) per patient

  6. Phase 1b Combination Therapy (Part 1: Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D) of rezatapopt when administered in combination with pembrolizumab

    RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data

    Measured: 18 months

  7. 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

    Number of participants with treatment related adverse events

    Measured: 12 months for treatment arm

  8. Phase 2 Monotherapy (Dose Expansion): Response rate assessment to evaluate the clinical activity / efficacy of rezatapopt

    Overall response rate in accordance with Response Evaluation Criteria (RECIST) v.1.1 as assessed by independent review across all cohorts

    Measured: 34 months

  9. Phase 2 Monotherapy (Dose Expansion): Response rate assessment to evaluate the clinical activity / efficacy of rezatapopt in ovarian cancer patients

    Overall response rate in accordance with Response Evaluation Criteria (RECIST) v.1.1 as assessed by independent review in the ovarian cancer cohort

    Measured: 34 months

Secondary outcomes (45)

  1. Phase 1 Monotherapy: PK profile of rezatapopt - Peak concentration (Cmax)

    Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt

    Measured: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

  2. Phase 1 Monotherapy: PK profile of rezatapopt - Time of peak concentration (Tmax)

    Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt

    Measured: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

  3. 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)

    Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt

    Measured: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

  4. Phase 1 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve in one dosing interval (AUCtau)

    Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt

    Measured: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

  5. Phase 1 Monotherapy: PK profile of rezatapopt - Trough observed concentrations (Ctrough/Ctau)

    Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt

    Measured: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

  6. Phase 1 Monotherapy: Blood plasma assessment to describe the concentration of PC14586 and metabolites when rezatapopt is administered orally.

    Blood plasma concentration

    Measured: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

  7. Phase 1 Monotherapy (Dose Escalation): Overall Response Rate per RECIST v1.1 or PCWG3 modified RECIST v1.1

    Evaluation of preliminary anti-tumor activity of rezatapopt as a single agent

    Measured: 41 months for study (end of Phase 1)

  8. Phase 1 Monotherapy (Dose Escalation): Time to Response per RECIST v1.1 or PCWG3 modified RECIST v1.1

    Evaluation of preliminary anti-tumor activity of rezatapopt as a single agent

    Measured: 41 months for study (end of Phase 1)

  9. Phase 1 Monotherapy (Dose Escalation): Duration of Response per RECIST v1.1 or PCWG3 modified RECIST v1.1

    Evaluation of preliminary anti-tumor activity of rezatapopt as a single agent

    Measured: 41 months for study (end of Phase 1)

  10. Phase 1 Monotherapy (Dose Escalation): Disease Control Rate per RECIST v1.1 or PCWG3 modified RECIST v1.1

    Evaluation of preliminary anti-tumor activity of rezatapopt as a single agent

    Measured: 41 months for study (end of Phase 1)

  11. Phase 1 Monotherapy (Dose Escalation): Progression Free Survival per RECIST v1.1 or PCWG3 modified RECIST v1.1

    Evaluation of preliminary anti-tumor activity of rezatapopt as a single agent

    Measured: 41 months for study (end of Phase 1)

  12. Phase 1 Monotherapy (Dose Escalation): Overall Survival

    Evaluation of preliminary anti-tumor activity of rezatapopt as a single agent

    Measured: 41 months for study (end of Phase 1)

  13. Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Peak concentration (Cmax)

    Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt

    Measured: Approximately 12 months per patient (30 months for treatment arm)

  14. Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Time of peak concentration (Tmax)

    Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt

    Measured: Approximately 12 months per patient (30 months for treatment arm)

  15. 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)

    Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt

    Measured: Approximately 12 months per patient (30 months for treatment arm)

  16. Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Area under the plasma concentration-time curve in one dosing interval (AUCtau)

    Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt

    Measured: Approximately 12 months per patient (30 months for treatment arm)

  17. Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Trough observed concentrations (Ctrough/Ctau)

    Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt

    Measured: Approximately 12 months per patient (30 months for treatment arm)

  18. Phase 1b Combination Therapy: Blood plasma assessment to describe the concentration of rezatapopt and metabolites when rezatapopt is administered orally in combination with pembrolizumab.

    Blood plasma concentration

    Measured: Approximately 12 months per patient (30 months for treatment arm)

  19. Phase 1b Combination Therapy: Overall Response Rate per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review

    Evaluation of anti-tumor activity of rezatapopt in combination with pembrolizumab

    Measured: 30 months for study (end of Phase 1b)

  20. Phase 1b Combination Therapy: Time to Response per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review

    Evaluation of anti-tumor activity of rezatapopt in combination with pembrolizumab

    Measured: 30 months for study (end of Phase 1b)

  21. Phase 1b Combination Therapy: Duration of Response per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review

    Evaluation of anti-tumor activity of rezatapopt in combination with pembrolizumab

    Measured: 30 months for study (end of Phase 1b)

  22. Phase 1b Combination Therapy: Disease Control Rate per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review

    Evaluation of anti-tumor activity of rezatapopt in combination with pembrolizumab

    Measured: 30 months for study (end of Phase 1b)

  23. Phase 1b Combination Therapy: Overall Survival

    Evaluation of anti-tumor activity of rezatapopt in combination with pembrolizumab

    Measured: 30 months for study (end of Phase 1b)

  24. Phase 1b Combination Therapy: Determine the number and type of adverse events to characterize the safety of rezatapopt

    Number of participants with treatment related adverse events

    Measured: 30 months for study (end of Phase 1b)

  25. Phase 1b Combination Therapy: Progression Free Survival per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review

    Evaluation of anti-tumor activity of rezatapopt in combination with pembrolizumab

    Measured: 30 months for study (end of Phase 1b)

  26. Phase 2 Monotherapy: PK profile of rezatapopt - Time of peak concentration (Tmax)

    Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt

    Measured: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

  27. Phase 2 Monotherapy: PK profile of rezatapopt - Peak concentration (Cmax)

    Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt

    Measured: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

  28. 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)

    Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt

    Measured: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

  29. Phase 2 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve in one dosing interval (AUCtau)

    Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt

    Measured: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

  30. Phase 2 Monotherapy: PK profile of rezatapopt - Trough observed concentrations (Ctrough/Ctau)

    Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt

    Measured: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

  31. Phase 2 Monotherapy: Blood plasma assessment to describe the concentration of rezatapopt and metabolites when rezatapopt is administered orally.

    Blood plasma concentration

    Measured: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

  32. Phase 2 Monotherapy (Dose Expansion): Determine the number and type of adverse events to characterize the safety of rezatapopt

    Number of participants with treatment related adverse events

    Measured: 34 months for study (end of Phase 2)

  33. Phase 2 Monotherapy (Dose Expansion): Overall Response Rate across all cohorts per RECIST v1.1 as assessed by Investigator

    Evaluation of anti-tumor activity of rezatapopt as a single agent

    Measured: 34 months for study (end of Phase 2)

  34. Phase 2 Monotherapy (Dose Expansion): Overall Response Rate in ovarian cancer cohort per RECIST v1.1 as assessed by Investigator

    Evaluation of anti-tumor activity of rezatapopt as a single agent

    Measured: 34 months for study (end of Phase 2)

  35. 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

    Evaluation of anti-tumor activity of rezatapopt as a single agent

    Measured: 34 months for study (end of Phase 2)

  36. 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

    Evaluation of anti-tumor activity of rezatapopt as a single agent

    Measured: 34 months for study (end of Phase 2)

  37. 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

    Evaluation of anti-tumor activity of rezatapopt as a single agent

    Measured: 34 months for study (end of Phase 2)

  38. 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

    Evaluation of anti-tumor activity of rezatapopt as a single agent

    Measured: 34 months for study (end of Phase 2)

  39. 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

    Evaluation of anti-tumor activity of rezatapopt as a single agent

    Measured: 34 months for study (end of Phase 2)

  40. 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

    Evaluation of anti-tumor activity of rezatapopt as a single agent

    Measured: 34 months for study (end of Phase 2)

  41. 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

    Evaluation of anti-tumor activity of rezatapopt as a single agent

    Measured: 34 months for study (end of Phase 2)

  42. 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

    Evaluation of anti-tumor activity of rezatapopt as a single agent

    Measured: 34 months for study (end of Phase 2)

  43. Phase 2 Monotherapy (Dose Expansion): Overall Survival in ovarian cancer cohort

    Evaluation of anti-tumor activity of rezatapopt as a single agent

    Measured: 34 months for study (end of Phase 2)

  44. Phase 2 Monotherapy (Dose Expansion): Overall Survival across all cohorts

    Evaluation of anti-tumor activity of rezatapopt as a single agent

    Measured: 34 months for study (end of Phase 2)

  45. Phase 2 Monotherapy (Dose Expansion): Quality of life assessment

    Changes from baseline in quality of life as measured by a validated instrument, for participants 18 and older

    Measured: Evaluated at every visit. 34 months for treatment arm (end of Phase 2)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Oct 2020
  2. Study start29 Oct 2020
  3. Primary completion15 Dec 2026 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
During Phase 2 Monotherapy, 2000mg QD of PC14586 (INN: rezatapopt) will be assigned to all participants. Participants will be assigned to one of five cohorts: ovarian cancer, lung cancer, breast cancer, endometrial cancer, or other solid tumors. Enrollment ongoing. During Phase 1 Monotherapy (Dose Escalation), participants will be assigned a dose level using an accelerated titration design in the initial dose cohorts, followed by a modified toxicity probability interval (mTPI) design in subsequent dose cohorts. Enrollment closed. During Part 1 of the Ph 1b Combination Therapy, patients will be assigned a dose level using mTPI design. A recommended rezatapopt Phase 2 Dose (RP2D) when administered in combination with pembrolizumab will be selected at the end of Phase 1b Part 1, and the RP2D will be assigned to all participants in Part 2. Enrollment closed.
Masking
None (open label)
Enrolment
300 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04585750
Sponsor's protocol ID
PMV-586-101
Other IDs
KEYNOTE-D79, MK-3475-D79
Status last verified
Oct 2026
First submitted
1 Oct 2020
Last updated
2 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Dumbrava EE, Shapiro GI, Parikh AR, Johnson ML, Tolcher AW, Thompson JA, El-Khoueiry AB, Vandross AL, Kummar S, Shepard DR, LeDuke K, Sheehan L, Alland L, Haque A, Jalota D, Fellous M, Schram AM. Phase 1 Study of Rezatapopt, a p53 Reactivator, in TP53 Y220C-Mutated Tumors. N Engl J Med. 2026 Feb 26;394(9):872-883. doi: 10.1056/NEJMoa2508820.

    PubMed 41740031

  • Schram AM, Fellous M, LeDuke K, Schmid A, Dumbrava EE. PYNNACLE phase II clinical trial protocol: rezatapopt (PC14586) monotherapy in advanced or metastatic solid tumors with a TP53 Y220C mutation. Future Oncol. 2025 Oct;21(24):3159-3166. doi: 10.1080/14796694.2025.2557176. Epub 2025 Sep 11.

    PubMed 40932470

  • Papavassiliou KA, Vassiliou AG, Papavassiliou AG. Rezatapopt: A promising small-molecule "refolder" specific for TP53Y220C mutant tumors. Neoplasia. 2025 Sep;67:101201. doi: 10.1016/j.neo.2025.101201. Epub 2025 Jun 20.

    PubMed 40543428

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing rezatapopt and pembrolizumab in people with Advanced Solid Tumor and Advanced Malignant Neoplasm, run by PMV Pharmaceuticals, Inc at 76 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 76 sites in United States, France, Italy, Spain, Australia and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact PMV Pharma Clinical Study Information Center ((609) 235-4038, clinicaltrials@pmvpharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt (time frame: 40 months). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04585750, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.

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