Clinical trial • Phase I/II • Oncology

PC14586 for Solid tumours with TP53 Y220C mutation (locally advanced or metastatic)

Phase I/II trial of PC14586 for Solid tumours with TP53 Y220C mutation (locally advanced or metastatic). open-label. 60 participants.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Solid tumours with TP53 Y220C mutation (locally advanced or metastatic)
Trial Stage
Phase I/II
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
24-01-2024
First CTIS Authorization Date
24-04-2024

Trial design

open-label Phase I/II trial in France, Italy, Germany and others.

Open Label
Yes
Biomarker Stratified
True, biomarker: TP53 Y220C mutation; strata: tumour-type cohorts (multiple tumour-specific cohorts including ovarian cohort)
Target Sample Size
60

Eligibility

Recruits 60 The record indicates 'isVulnerablePopulationSelected': true. Informed consent must be provided as written, signed and dated informed consent by the patient prior to any mandatory study-specific procedures (see Inclusion criterion #2). Specific subject information and informed consent forms are provided for subgroups (e.g., Pregnant-Partner or Patient ICF, Newborn ICF, PK Sampling ICF, Pregnancy Follow-Up ICF) and are available in multiple languages (documents listed in French, Italian, German, Spanish and English). No under-18 assent is applicable because minimum age is 18..

Pregnancy Exclusion
8. Female patients of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to first dose of study drug or be of non-childbearing potential. Non-childbearing potential is defined as: • Postmenopausal, defined as no menses for 12 months without an alternative medical cause. A follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormone replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. • Surgically sterile.
Vulnerable Population
The record indicates 'isVulnerablePopulationSelected': true. Informed consent must be provided as written, signed and dated informed consent by the patient prior to any mandatory study-specific procedures (see Inclusion criterion #2). Specific subject information and informed consent forms are provided for subgroups (e.g., Pregnant-Partner or Patient ICF, Newborn ICF, PK Sampling ICF, Pregnancy Follow-Up ICF) and are available in multiple languages (documents listed in French, Italian, German, Spanish and English). No under-18 assent is applicable because minimum age is 18.

Inclusion criteria

  • {"criterion_text":"- 1. Patient is at least 18 years of age.\n- 10.Patients who are males and have a female partner of childbearing potential must (1) use a condom, both for contraception and to protect any existing pregnancy and should also be advised of the benefit for a female partner to use a highly effective method of contraception, as described in inclusion criterion #9, or (2) agree to be abstinent from heterosexual intercourse as their preferred and usual lifestyle. These requirements should be followed starting with the first dose of study drug through 3 months after the last dose of study drug. Refer to Appendix 2 for contraceptive guidance.\n- 11. Patients must be willing to undergo a tumor biopsy during screening for NGS if an archival tumor specimen is not available and if the procedure is in line with standard of care (i.e., of low risk to patient and the tumor is of sufficient size to be biopsied).\n- 12. Patient has a life expectancy of at least 3 months as assessed by the Investigator.\n- 13. Measurable disease per RECIST v1.1 as assessed by the Investigator, with the last imaging performed within 28 days before C1D1.\n- 2. Patient understands the study procedures and agrees to participate by giving written, signed, and dated informed consent prior to any mandatory study-specific procedures, sampling, or analysis.\n- 3. Patient has an ECOG status of 0 or 1\n- 4. Patient has a histologically or cytologically confirmed locally advanced or metastatic solid malignancy with a TP53 Y220C mutation identified by an analytical validated assay in a certified testing laboratory.\n- 5. Patients must have received prior standard therapy appropriate for their tumor type and stage of disease and have documented radiographic progression during or after their most recent line of anticancer therapy, or in the opinion of the Investigator are ineligible for appropriate standard of care therapy. 5a. Patients with ovarian cancer must be platinum resistant defined as disease progressing within 6 months of platinum-based chemotherapy or platinum-refractory defined as disease progressing during therapy or within 4 weeks after last dose.\n- 6. Patients with CRPC must have ongoing androgen deprivation therapy with a gonadotropin-releasing hormone analog or inhibitor, or orchiectomy (medical or surgical castration).\n- 7. Patient has adequate organ function as defined as: • Hepatic: total bilirubin ≤ 1.5 x upper limit of normal (ULN) or for patients with Gilbert’s syndrome, direct bilirubin ≤ 1.5 x ULN, ALT and AST ≤ 3.0 x ULN for patients without liver metastasis and ≤ 5.0 x ULN for patients with liver metastasis; albumin > 3g/dl. • Renal: Estimated Glomerular Filtration Rate (eGFR) must be ≥ 40 mL/min. •Hematological: ANC ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, and hemoglobin ≥ 9 g/dL. • Serum potassium, calcium, magnesium, and phosphorus within normal limits or ≤ Grade 1. If values are low on the initial screening assessment, supplements may be given and values repeated to confirm within normal limits or ≤ Grade 1.\n- 8. Female patients of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to first dose of study drug or be of non-childbearing potential. Non-childbearing potential is defined as: • Postmenopausal, defined as no menses for 12 months without an alternative medical cause. A follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormone replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. • Surgically sterile.\n- 9. Patients who are females of childbearing potential must use a highly effective method of contraception for the course of the study or be abstinent from 14 days prior to the first dose of study drug through 3 months after the last dose of study drug .Highly effective methods of contraception include (1) oral, injected, or implanted hormonal methods of contraception that inhibit ovulation, (2) intrauterine device, (3) intrauterine hormone-releasing system, (4) bilateral tubal occlusion/ligation, (5) vasectomized partner with verified absence of sperm in ejaculate post-vasectomy. Barrier contraception (including male and female condoms with or without spermicide) is not considered a highly effective method of contraception. If used, this method must be used in combination with another acceptable method listed above. Refer to Appendix 2 for contraceptive guidance. For patients with breast cancer, the following methods of contraception are not acceptable, and an alternative form of contraception should be used: •\tOral, injected, or implanted hormonal methods of contraception •\tIntrauterine hormone-releasing systems Instead, patients with breast cancer should use one of the following highly effective methods of contraception: •\tIntrauterine device •\tBilateral tubal occlusion/ligation •\tVasectomized partner with verified absence of sperm in ejaculate post-vasectomy"}

Exclusion criteria

  • {"criterion_text":"- 1. Patient has received prior chemotherapy, targeted therapy, immunotherapy, or treatment with an investigational anticancer agent within 21 days or 5 half-lives (if half-life is known), whichever is shorter, before receiving their first dose of study drug.\n- 18. Patient has a known or suspected hypersensitivity to rezatapopt or any of its excipients.\n- 2. Patient has received radiotherapy within 14 days.\n- 3. Patient has a primary CNS tumor.\n- 4. Patient has history of leptomeningeal disease or spinal cord compression.\n- 5. Patient has brain metastases. Exception: Patients with brain metastases are permitted if they are neurologically stable and do not require steroids to treat associated neurological symptoms.\n- 6. Patient has had a stroke or transient ischemic attack within 6 months prior to screening.\n- 7. Patient has had one or more of the following cardiac criteria: • Unstable angina within 6 months prior to screening • Myocardial infarction within 6 months prior to screening • New York Heart Association Class II or greater congestive heart failure • QT interval corrected (QTc) using Fridericia’s formula (QTcF) > 470 msec obtained as the mean from 3 consecutive resting ECGs. Exception: A QTcF value corrected for wide QRS > 120 msec (QTcFBBB) should be used in place of QTcF for patients with non-clinically significant wide QRS > 120 msec due to a pacemaker or bundle branch block • Clinically significant abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block) • Congenital long QT syndrome • Uncontrolled hypertension\n- 8. Patient treated with any of the following medications prior to receiving rezatapopt within the below time windows: • Strong CYP3A4 inducers within 14 days of first dose of rezatapopt • Strong CYP2C9 inhibitors/inducers within 14 days of first dose of rezatapopt\n- 9. Patient has a history of GI disease that may interfere with absorption of study drug (e.g., ulcerative colitis, Crohn’s disease, repeat bowel obstruction, significant nausea or frequent vomiting, severe GERD, severe diarrhea, malabsorption syndrome, or small bowel/gastric resection).\n- 19.\tPatient whose tumor harbors a known KRAS mutation, defined as a single nucleotide variant (SNV).\n- 10. Patient with dysphagia that could interfere with the ability to swallow tablets.\n- 11. Patient has a history of prior organ transplant.\n- 12. Patient has any medical condition that would, in the Investigator’s judgment, prevent the patient’s participation in the clinical study due to safety concerns or compliance with clinical study procedures.\n- 13. Patient has any other known, active malignancy, except for treated cervical intraepithelial neoplasia, or non-melanoma skin cancer.\n- 14. Patient has a known, active uncontrolled Hepatitis B infection (i.e., viral load above the limit of quantification), Hepatitis C infection (i.e., viral load above the limit of quantification), or human immunodeficiency virus infection (viral load > 400 copies/mL). Patients whose viral load is controlled should be on established antiretroviral therapy for at least 4 weeks prior to receiving their first dose of rezatapopt.\n- 15. Female patients that are breastfeeding or bottle feeding with their breast milk.\n- 16. Patient has any unresolved toxicities from prior anti-cancer therapy greater than Grade 1 at the time of starting rezatapopt treatment with the exception of alopecia and Grade 2 prior chemotherapy induced neuropathy.\n- 17. Patient has had major surgery within 2 weeks prior to the planned start of rezatapopt treatment."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 1. Overall Response Rate (ORR) per Blinded Independent Central Review (BICR) assessment (RECIST v1.1) across all cohorts.","definition_or_measurement_approach":"Measured by RECIST v1.1 assessed by Blinded Independent Central Review (BICR)."}
  • {"endpoint_text":"- 2. ORR per BICR assessment (RECIST v1.1) in ovarian cancer cohort.","definition_or_measurement_approach":"Measured by RECIST v1.1 assessed by Blinded Independent Central Review (BICR) in the ovarian cancer cohort."}

Secondary endpoints

  • {"endpoint_text":"- 1. ORR across all cohorts- RECIST v1.1 as assessed by Investigator","definition_or_measurement_approach":"Measured by RECIST v1.1 as assessed by Investigator."}
  • {"endpoint_text":"- 2. ORR in ovarian cancer cohort - RECIST v1.1 as assessed by Investigator","definition_or_measurement_approach":"Measured by RECIST v1.1 as assessed by Investigator in the ovarian cancer cohort."}
  • {"endpoint_text":"- 3. Incidence of AEs and SAEs, and changes between baseline and post-baseline laboratory assessments, ECGs, ECOG performance status, vital signs, and physical exams. Toxicities will be graded using CTCAE v5.0 (NCI, 2017)","definition_or_measurement_approach":"Safety assessed by incidence of AEs/SAEs and changes in labs, ECGs, ECOG, vitals and physical exams; toxicities graded per CTCAE v5.0 (NCI, 2017)."}
  • {"endpoint_text":"- 4. TTR, DoR, DCR at 6, 12, 18, and 24 weeks, PFS across all cohorts and in ovarian cancer only - RECIST v1.1 as assessed by BICR - RECIST v1.1 as assessed by Investigator","definition_or_measurement_approach":"Time-to-response (TTR), Duration of Response (DoR), Disease control rate (DCR) at specified timepoints and PFS measured by RECIST v1.1 assessed by BICR and by Investigator."}
  • {"endpoint_text":"- 5. OS across all cohorts and in ovarian cancer only","definition_or_measurement_approach":"Overall survival measured as time from baseline to death."}
  • {"endpoint_text":"- 6. Rezatapopt concentrations (and concentrations of metabolites)","definition_or_measurement_approach":"Measurement of rezatapopt and metabolite concentrations in plasma (bioanalysis)."}
  • {"endpoint_text":"- 7. Plasma PK parameters: Cmax, Tmax, AUC0-t, AUCtau, Ctrough/Ctau","definition_or_measurement_approach":"Pharmacokinetic parameters measured from plasma concentration-time data (Cmax, Tmax, AUC0-t, AUCtau, Ctrough/Ctau)."}
  • {"endpoint_text":"- 8. EORTC QLQ-C30","definition_or_measurement_approach":"Quality of life assessed using the EORTC QLQ-C30 questionnaire."}

Recruitment

Digital Remote Recruitment
True, digital methods include the PYNNACLE patient webpages (country-specific), Medidata Patient Cloud App standard screens, electronic subject diary and ePRO (EORTC QLQ-C30) in multiple languages (DE, FR, ES, IT, EN).
Planned Sample Size
60
Recruitment Window Months
35
Consent Approach
Written, signed and dated informed consent required from the participant prior to any mandatory study-specific procedures (Inclusion criterion #2). Specific informed consent forms are provided for subgroups (e.g., Pregnant-Partner or Patient ICF, Newborn ICF, PK Sampling ICF, Pregnancy Follow-Up ICF). Consent documentation is available in multiple languages (documents listed in French, Italian, German, Spanish and English).

Methods

  • Site-based recruitment at participating oncology centres (site lists and contact details provided in Part II submissions).
  • PYNNACLE patient webpage used for patient-facing information and recruitment (country-specific patient webpage documents listed for FR, IT, DE, ES).
  • Country-specific 'Recruitment and Informed Consent Procedure' documents (K1) provided (examples: France, Italy, Germany, Spain).
  • GP letter (Italy) to inform local physicians (document K2_PMV-586-101_GP-Letter_IT_Italian_Public).
  • Use of Medidata Patient Cloud App and electronic subject diaries / ePRO (QLQ-C30) to support remote data capture (documents listed).

Geography

Total Number Of Sites
30
Total Number Of Participants
105

France

Earliest CTIS Part Ii Submission Date
08-04-2024
Latest Decision Or Authorization Date
18-03-2026
Processing Time Days
709
Number Of Sites
9
Number Of Participants
40

Sites

Site Name
Institut De Cancerologie De Lorraine
Department Name
Oncologie Médicale
Contact Person Name
Aurélien LAMBERT
Contact Person Email
a.lambert@nancy.unicancer.fr
Site Name
Institut Bergonie
Department Name
Département d‘Oncologie médicale
Contact Person Name
Véronique DEBIEN
Contact Person Email
v.debien@bordeaux.unicancer.fr
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Oncologie médicale
Contact Person Name
Lauriane EBERST
Contact Person Email
l.eberst@icans.eu
Site Name
Centre Hospitalier Universitaire De Nimes
Department Name
Oncologie Médicale
Contact Person Name
Frédéric FITENI
Contact Person Email
frederic.fiteni@chu-nimes.fr
Site Name
Institut De Cancerologie De L Ouest
Department Name
Oncologie médicale
Contact Person Name
Jean-Sebastien FRENEL
Site Name
Institut Universitaire Du Cancer Toulouse-Oncopole
Department Name
Département d'Oncologie Médicale
Contact Person Name
Carlos GOMEZ-ROCA
Site Name
Institut Gustave Roussy
Department Name
Département d’Innovation Thérapeutique et des Essais Précoces (DITEP)
Contact Person Name
Yohann LORIOT
Contact Person Email
yohann.loriot@gustaveroussy.fr
Site Name
Centre Jean Perrin
Department Name
Service d’oncologie
Contact Person Name
Xavier DURANDO
Site Name
Centre Leon Berard
Department Name
Oncologie médicale
Contact Person Name
Isabelle RAY-COQUARD

Italy

Earliest CTIS Part Ii Submission Date
10-04-2024
Latest Decision Or Authorization Date
25-03-2026
Processing Time Days
714
Number Of Sites
9
Number Of Participants
35

Sites

Site Name
Humanitas Mirasole S.p.A.
Contact Person Name
Domenica Lorusso
Contact Person Email
domenica.lorusso@hunimed.eu
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
S.C. Oncologia Medica
Contact Person Name
Massimo Di Nicola
Site Name
I.F.O. Istituti Fisioterapici Ospitalieri
Department Name
UOSD Sperimentazioni cliniche: Fase 1 e medicina di precisione
Contact Person Name
Lorenza Landi
Contact Person Email
lorenza.landi@ifo.it
Site Name
Azienda Ospedaliera Ospedale Niguarda Ca Granda
Department Name
Oncologia Medica Falck
Contact Person Name
Salvatore Siena
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
Gynecologic Oncology Unit
Contact Person Name
Anna Fagotti
Site Name
European Institute Of Oncology S.r.l.
Department Name
Divisione Sviluppo Nuovi Farmaci per Terapie Innovative
Contact Person Name
Giusepe Curigliano
Contact Person Email
Giuseppe.curigliano@ieo.it
Site Name
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Department Name
SC Oncologia Sperimentale Uro-Ginecologica
Contact Person Name
Anna Passarelli
Site Name
Istituto Di Candiolo Fondazione Del Piemonte Per Loncologia IRCCS
Department Name
Oncologia medica
Contact Person Name
Chiara Lazzari
Contact Person Email
chiara.lazzari@ircc.it
Site Name
Humanitas Research Hospital
Department Name
Operative unit of Oncology and Hematology
Contact Person Name
Armando Santoro

Germany

Earliest CTIS Part Ii Submission Date
01-04-2024
Latest Decision Or Authorization Date
23-03-2026
Processing Time Days
721
Number Of Sites
5
Number Of Participants
15

Sites

Site Name
Universitaetsklinikum Augsburg
Department Name
II. Medizinische Klinik
Contact Person Name
Rainer Claus
Contact Person Email
rainer.claus@uk-augsburg.de
Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Nationales Centrum für Tumorerkrankungen (NCT)
Contact Person Name
Georg Martin Haag
Site Name
Asklepios Kliniken Hamburg GmbH
Department Name
Asklepios Klinik Altona Abteilung Onkologie, Hämatologie
Contact Person Name
Dirk Arnold
Contact Person Email
d.arnold@asklepios.com
Site Name
Universitaetsklinikum Essen AöR
Department Name
Westdeutsches Tumorzentrum
Contact Person Name
Marcel Wiesweg
Contact Person Email
marcel.wiesweg@uk-essen.de
Site Name
Goethe University Frankfurt
Department Name
Medizinische Klinik II Hämatologie/Onkologie
Contact Person Name
Martin Sebastian
Contact Person Email
sebastian@med.uni-frankfurt.de

Spain

Earliest CTIS Part Ii Submission Date
06-02-2024
Latest Decision Or Authorization Date
23-03-2026
Processing Time Days
776
Number Of Sites
7
Number Of Participants
15

Sites

Site Name
Fundacion Rioja Salud
Department Name
Oncology
Contact Person Name
María José de Miguel Luken
Contact Person Email
maria.demiguel@startrioja.com
Site Name
Hospital Clinico Universitario De Valencia
Department Name
Oncology
Contact Person Name
José Alejandro Pérez Fidalgo
Contact Person Email
japfidalgo@msn.com
Site Name
Hospital Quironsalud Barcelona
Department Name
Oncology
Contact Person Name
Elena Garralda Cabanas
Contact Person Email
egarralda@nextoncology.eu
Site Name
Hospital Universitario Hm Sanchinarro
Department Name
Oncology
Contact Person Name
Irene Moreno Candilejo
Contact Person Email
irene.moreno@startmadrid.com
Site Name
Hospital Universitari Vall D Hebron
Department Name
Medical Oncology
Contact Person Name
Lorena Fariñas Madrid
Contact Person Email
lfarinas@vhio.net
Site Name
Hospital Universitario 12 De Octubre
Department Name
Oncology
Contact Person Name
Santiago Ponce Aix
Contact Person Email
santiago.ponce@oncosur.org
Site Name
Hospital Universitario Fundacion Jimenez Diaz
Department Name
Oncology
Contact Person Name
Víctor Moreno García
Contact Person Email
victor.moreno@startmadrid.com

Sponsor

Primary sponsor

Full Name
PMV Pharmaceuticals Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
PPD Development LP
Responsibilities
codes: 1,10,11,12,2,5,7,8 (multiple operational roles listed)
Name
Catalyst Clinical Research LLC
Responsibilities
code 8
Name
Bioclinica Inc.
Responsibilities
code 4
Name
Inotiv Inc.
Responsibilities
code 4

Third parties

  • {"country":"United States","full_name":"Q2 Solutions LLC","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Preventiongenetics LLC","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Neogenomics Laboratories Inc.","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Acm Medical Laboratory Inc.","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Labconnect LLC","duties_or_roles":"Sample Storage (code 15); code 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Mayo Collaborative Services LLC","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Germany","full_name":"LabConnect GmbH","duties_or_roles":"Sample Storage (code 15); code 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United Kingdom","full_name":"Acm Global Central Laboratory Limited","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Catalyst Clinical Research LLC","duties_or_roles":"code 8","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Unisphere Travel Ltd. Inc.","duties_or_roles":"Travel and Reimbursement (code 15)","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Scisafe Inc.","duties_or_roles":"Long term storage (code 15)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Ambry Genetics Corp.","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Foundation Medicine, Inc","duties_or_roles":"Sample Storage (code 15); code 4","organisation_type":"Health care"}
  • {"country":"United States","full_name":"Inotiv Inc.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"codes: 1,10,11,12,2,5,7,8 (multiple operational roles listed)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Infinity Biologix LLC","duties_or_roles":"Pharmacogenomics (code 15)","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
PC14586 (rezatapopt)
Active Substance
PC14586
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Starting Dose
2000 mg
Dose Levels
2000 mg (Phase 2 dose expansion described as 2000 mg QD for cohorts)
Frequency
Once daily (QD) with food

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