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Evaluating PC14586 for advanced solid tumors with a specific mutation

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)

PHASE1; PHASE2 · PMV Pharmaceuticals, Inc · NCT04585750

This study is testing a new oral medication called PC14586 to see if it can help people with advanced solid tumors that have a specific mutation in the TP53 gene.

Quick facts

PhasePHASE1; PHASE2
Study typeInterventional
Enrollment300 (estimated)
Ages12 Years and up
SexAll
SponsorPMV Pharmaceuticals, Inc (industry)
Drugs / interventionspembrolizumab, radiation
Locations76 sites (Irvine, California and 75 other locations)
Trial IDNCT04585750 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of PC14586, a novel oral small molecule designed to reactivate the p53 protein, in patients with advanced solid tumors that have a TP53 Y220C mutation. The study consists of two phases: Phase 1 focuses on determining the maximum tolerated dose and preliminary efficacy of PC14586, while Phase 2 assesses its effectiveness as a monotherapy in various cancer cohorts. Additionally, there is a Phase 1b component that explores the combination of PC14586 with pembrolizumab, an immune checkpoint inhibitor. Enrollment is currently open for the Phase 2 portion of the study.

Who should consider this trial

Good fit: Ideal candidates include adults and adolescents with locally advanced or metastatic solid tumors that have the TP53 Y220C mutation and have previously undergone anticancer therapy.

Not a fit: Patients with primary CNS tumors, recent anti-cancer therapy, or those with certain neurological conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors harboring the TP53 Y220C mutation.

How similar studies have performed: While this approach is novel in targeting the TP53 Y220C mutation specifically, similar studies targeting p53 reactivation have shown promise in other contexts.

Eligibility criteria

Show full inclusion / exclusion criteria 
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)

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

Where this trial is running

Irvine, California and 75 other locations

+26 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Advanced Solid Tumor, Advanced Malignant Neoplasm, Metastatic Cancer, Metastatic Solid Tumor, Lung Cancer, Ovarian Cancer, Endometrial Cancer, Prostate Cancer

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.