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Taking people in ItalyPhase 1/2

Tests rezatapopt in advanced solid tumors with a TP53 Y220C mutation

Tests rezatapopt, alone or with pembrolizumab, in people with advanced TP53 Y220C tumors.

Key facts

Who runs it
PMV Pharmaceuticals, Inc
Where
Candiolo, Milan, Naples, Rome, and Rozzano, ItalySee the 9 sitesAlso in 8 other countries, 67 sites
Trial code
Registry title
The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)
Status
Recruiting
Phase
Phase 1/2
People taking part
300 people, planned
Started
29 Oct 2020
Expected to end
31 Dec 2027
Type of study
Interventional, 9 groups
Treatments tested
  • rezatapopt
  • pembrolizumab
Record updated
2 October 2026

Who can take part

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for adults, and some teenagers, with advanced or spreading solid tumors that carry a TP53 Y220C mutation and have grown after earlier treatment.

Age
18 years or older. Ages 12 to 17 only after Safety Review Committee approval.
Sex
All sexes can join.
Disease stage
Locally advanced or metastatic solid tumor. Measurable disease per RECIST v1.1 is needed in Phase 2. ECOG status of 0 or 1.
Earlier treatment
Must have had one or more earlier lines of anticancer therapy and the disease has grown. For the pembrolizumab combination (Phase 1b): never had anti-PD-1/PD-L1 treatment, or the disease grew on it.
Biomarker or test result
TP53 Y220C mutation. In Phase 2, people with a known KRAS mutation cannot join, except ovarian cancer patients with a known KRAS SNV.

Main reasons for not taking part

  • Primary tumor of the brain or spinal cord (CNS)
  • Brain metastases, unless stable and no steroids are needed
  • Serious heart problems, or stroke or mini-stroke within 6 months
  • Earlier organ transplant
  • Known active, uncontrolled hepatitis B, hepatitis C or HIV infection

The registry criteria, word for word

Show all 31 criteriaShow less

Who can take part

  • 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

Who cannot take part

  • Anti-cancer therapy within 21 days (or 5 half-lives) of receiving the study drug
  • Radiotherapy within 14 days of receiving the study drug
  • 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
  • Strong CYP3A4 inducers and strong CYP2C9 inhibitors/inducers within 14 days of first dose of rezatapopt
  • History of prior organ transplant
  • 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
  • Has previously received rezatapopt
  • History of leptomeningeal disease or spinal cord compression
  • History of gastrointestinal (GI) disease that may interfere with absorption of study drug or patients unable to take oral medication
  • 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)
  • 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
  • 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
  • Primary CNS tumor

Where in Italy

Also in 8 other countries, 67 sites

  • Fondazione del Piemonte per l'Oncologia (IRCCS)Candiolo, ItalyContact: Chiara Lazzari, MDTaking people
  • ASST Grande Ospedale Metropolitano NiguardaMilan, ItalyContact: Salvatore Siena, MDTaking people
  • Fondazione IRCCS - Istituto Nazionale dei TumoriMilan, ItalyContact: Massimo Di Nicola, MDTaking people
  • Humanitas San Pio XMilan, ItalyContact: Domenica Lorusso, MDTaking people
  • Istituto Europeo di OncologiaMilan, ItalyContact: Giuseppe Curigliano, MDTaking people
  • IRCCS - lstituto Nazionale Tumori - Fondazione G. PascaleNaples, ItalyContact: Anna Passarelli, MDTaking people
  • Fondazione Policlinico Universitario Agostino Gemelli IRCCSRome, ItalyContact: Anna Fagotti, MDTaking people
  • Istituti Fisioterapici Ospitalieri - Istituto Nazionale Tumori Regina ElenaRome, ItalyContact: Lorenza Landi, MDTaking people
  • Istituto Clinico HumanitasRozzano, ItalyContact: Armando Santoro, MDTaking people

About the trial

What the trial wants to find out

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.

The 9 groups in the trial

  • Phase 1 Monotherapy Dose EscalationTreatment being tested

    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).

    Treatment: rezatapopt

  • Phase 1b Combination Therapy Dose Escalation, Part 1Treatment being tested

    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.

    Treatment: rezatapopt and pembrolizumab

  • Phase 1b Combination Therapy Dose Expansion, PD(L)-1 naive patientsTreatment being tested

    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.

    Treatment: rezatapopt and pembrolizumab

  • Phase 1b Combination Therapy Dose Expansion, PD(L)-1 relapsed/refractory patientsTreatment being tested

    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.

    Treatment: rezatapopt and pembrolizumab

  • Phase 2 Monotherapy Dose Expansion, Ovarian Cancer CohortTreatment being tested

    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.

    Treatment: rezatapopt

  • Phase 2 Monotherapy Dose Expansion, Lung Cancer CohortTreatment being tested

    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.

    Treatment: rezatapopt

  • Phase 2 Monotherapy Dose Expansion, Breast Cancer CohortTreatment being tested

    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.

    Treatment: rezatapopt

  • Phase 2 Monotherapy Dose Expansion, Endometrial Cancer CohortTreatment being tested

    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.

    Treatment: rezatapopt

  • Phase 2 Monotherapy Dose Expansion, Other Solid Tumors CohortTreatment being tested

    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.

    Treatment: rezatapopt

Questions to ask the study team

  1. How often do I need to come in, and for how long each time?
  2. Are travel costs paid?
  3. Can I keep my own doctor?
  4. What happens if I want to stop?

Contact the study team: see the registry record → Contacts and Locations

Print a page for my doctor

Data and sources

Registry record
Listed on ClinicalTrials.gov.
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)
Plain-language title
Tests rezatapopt in advanced solid tumors with a TP53 Y220C mutationGenerated from the registry record. The registry title is the official one.
AI summary
From the trial's eligibility criteria. Read by machine on 12 November 2026.
Record updated
2 October 2026