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PYNNACLE Study: Rezatapopt for Advanced Solid Tumors with TP53 Y220C Mutation

This study, called PYNNACLE, is testing a new oral drug called rezatapopt for people with advanced solid tumors that have a specific genetic change (mutation) called TP53 Y220C. Rezatapopt works by reactivating the p53 protein, which helps control cell growth. The study is also looking at rezatapopt in combination with another drug called pembrolizumab. To join, you must have a locally advanced or metastatic solid tumor with the TP53 Y220C mutation, have good general health, and have tried other cancer treatments. The study aims to see how safe rezatapopt is and how well it shrinks tumors. The Phase 2 part of the study, which evaluates how effective rezatapopt is on its own, is currently open for enrollment.

Study design
This is an interventional study with a planned enrollment of 300 participants. It has different phases, including a Phase 1 to find the right dose and a Phase 2 to evaluate effectiveness.
What's involved
Not specified in the trial record.
Compensation
Not stated in the trial record.
Follow-up
Safety of rezatapopt will be measured for 40 months. The recommended Phase 2 dose will be established within 30 months.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT04585750

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

Recruiting
PHASE1Ages 12+InterventionalTreatment
PMV Pharmaceuticals, Inc
~300 participants
Updated 2026-08-10 on ClinicalTrials.gov
What's tested:rezatapoptpembrolizumab

At a glance

Recruiting sites
72 of 77 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt
Measured over 40 months
+8 more outcomes measured

Conditions

Advanced Solid Tumor
Advanced Malignant Neoplasm
Metastatic Cancer
Metastatic Solid Tumor
Lung Cancer
Ovarian Cancer
Endometrial Cancer
Prostate Cancer
Colorectal Cancer
Breast Cancer
Other Cancer
Locally Advanced
Head and Neck Cancer
Gall Bladder Cancer
Small Cell Lung Cancer
Small Cell Lung Cancer ( SCLC )
Small Cell Lung Carcinoma
NSCLC
NSCLC (Non-small Cell Lung Cancer)
SCLC
Non-Small Cell Lung Carcinoma
Triple Negative Breast Cancer
TNBC
HER2+ Breast Cancer
Non-Small Cell Lung Cancer
ER/PR Positive Breast Cancer
HER2- Breast Cancer
HER2-positive Breast Cancer
HER2-negative Breast Cancer
ER/PR(+), Her2(-) Breast Cancer

Explore related trials

Breast CarcinomaColorectal CarcinomaEndometrial CarcinomaGallbladder Malignant NeoplasmLung CarcinomaMalignant Head and Neck NeoplasmMalignant Ovarian NeoplasmProstate CarcinomaSolid NeoplasmTP53 Gene

Where it's being run

77 sites across 47 states
Texas5
South Korea5
Spain5
California4
Lombardy4
Florida3
Pennsylvania3
France3

Study leadership

  • Marc Fellous, MD · STUDY_DIRECTOR · Sr. Vice President of Medical Affairs

Who to contact

PMV Pharma Clinical Study Information Center
[email protected]
(609) 235-4038
Email the study team

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Eligibility criteria

Inclusion

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)
Anti-PD-1/PD-L1 naive or must have progressed on treatment
Measurable disease

Exclusion

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
Known KRAS mutation, defined as a single nucleotide variant (SNV) (Phase 2)
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

What this trial measures

  • Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt40 months

    Number of participants with treatment related adverse events

  • Phase 1 Monotherapy (Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D)30 months

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

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

  • 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 pembrolizumab18 months for treatment arm

    Number of participants with treatment related adverse events

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

  • Phase 1b Combination Therapy (Part 1: Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D) of rezatapopt when administered in combination with pembrolizumab18 months

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

  • 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 pembrolizumab12 months for treatment arm

    Number of participants with treatment related adverse events

  • Phase 2 Monotherapy (Dose Expansion): Response rate assessment to evaluate the clinical activity / efficacy of rezatapopt34 months

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

  • Phase 2 Monotherapy (Dose Expansion): Response rate assessment to evaluate the clinical activity / efficacy of rezatapopt in ovarian cancer patients34 months

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