NCT04585750 · PMV Pharmaceuticals, Inc
The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)
What this study is about
The Phase 2 treatment given alone portion of this study is currently enrolling and will evaluate the effectiveness and safety of PC14586 (INN rezatapopt) in participants with locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation.
View original scientific description
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.
Interventions
DRUG
rezatapopt
First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.
DRUG
pembrolizumab
Participants receive pembrolizumab 200 mg by intravenous (IV) infusion over 30 minutes.
Primary outcome measures
Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt
Time frame: 40 months
Number of participants with treatment related adverse events
Phase 1 Monotherapy (Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D)
Time frame: 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)
Time frame: 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 pembrolizumab
Time frame: 18 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 pembrolizumab
Time frame: The 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 pembrolizumab
Time frame: 18 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 pembrolizumab
Time frame: 12 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 rezatapopt
Time frame: 34 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 patients
Time frame: 34 months
Overall response rate in accordance with Response Evaluation Criteria (RECIST) v.1.1 as assessed by independent review in the ovarian cancer cohort
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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 28 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 mo
Where
- Irvine, California
- La Jolla, California
- Los Angeles, California
- Denver, Colorado
- New Haven, Connecticut
- Newark, Delaware
- Miami, Florida
- Orlando, Florida
- Port Charlotte, Florida
- Boston, Massachusetts
- Detroit, Michigan
- Omaha, Nebraska
And 18 more locations — see the full list below.
Collaborators
Merck Sharp & Dohme LLC
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 26, 2026 · Source of record for eligibility and locations