RecruitingPhase 1/2

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

United States, Australia, France300 participantsStarted 2020-10-29

Plain-language summary

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.

Who can participate

Age range

12 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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 medi…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

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

Timeframe: 40 months

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

Timeframe: 30 months

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

Timeframe: The first 28 days of treatment (Cycle 1) per patient

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

Timeframe: 18 months for treatment arm

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

Timeframe: The first 28 days of combination treatment arm (starting on Day -7) per patient

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

Trial details

NCT IDNCT04585750

SponsorPMV Pharmaceuticals, Inc

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2026-08-15

Contact for this trial

PMV Pharma Clinical Study Information Center

(609) 235-4038 clinicaltrials@pmvpharma.com

View on ClinicalTrials.gov More Advanced Solid Tumor trials