Study objectives
The aim of the PYNNACLE study is to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of rezatapopt in patients with solid tumors that have a TP53 Y220C mutation, including but not limited to ovarian cancer, lung cancer, breast cancer, and endometrial cancer.
PYNNACLE is a Phase 1/2 clinical study
PYNNACLE (NCT04585750) is an ongoing open-label, multicenter Phase 1/2 clinical study of rezatapopt (on its own and in combination with pembrolizumab) in patients with locally advanced or metastatic solid tumors that have a TP53 Y220C mutation.
Rezatapopt is a first-in-class, oral, selective p53 reactivator, specific to TP53 Y220C.
The aims of the Phase 1 portion of this study were to find a suitable dose of rezatapopt, as well as assess pharmacokinetics, safety, and efficacy. Enrollment into the Phase 1 Monotherapy portion is complete.
The aim of the Phase 1b portion of the study was to evaluate rezatapopt in combination with pembrolizumab. Enrollment into the Phase 1b Combination therapy portion is complete.
The aims of the Phase 2 portion of the study are to assess the efficacy of rezatapopt on its own, as well as assessing safety, pharmacokinetics, and quality of life. This portion of the study is currently enrolling.
Patient eligibility criteria
The following eligibility criteria are applicable to the Phase 2 part of the study. For further information on eligibility criteria, please visit clinicaltrials.gov.
Inclusion criteria:
Patients with a locally advanced or metastatic solid tumor that harbors a TP53 Y220C mutation
Aged ≥18 years (all global sites except Singapore: ≥21 years and Republic of Korea: ≥19 years)
Adolescents 12–17 years of age if ≥40 kg in US, Australia, and Republic of Korea (12–18 years of age in Republic of Korea).
Previously treated with one or more lines of anticancer therapy
Eastern Cooperative Oncology Group performance status score of 0 or 1
Exclusion criteria:
Brain metastases, unless neurologically stable
History of leptomeningeal disease, spinal cord compression, organ transplant, or gastrointestinal disease which may impact study drug absorption
Primary central nervous system tumor
Heart conditions (unstable angina within 6 months prior to screening, uncontrolled hypertension, heart attack within 6 months prior to screening, heart failure or other clinically significant rhythm abnormalities)
Known KRAS mutation, defined as a single nucleotide variant
PYNNACLE clinical study locations
PYNNACLE is now enrolling patients with solid tumors that have a TP53 Y220C mutation at medical centers globally.
Further information on clinical studies
Your patient can learn more about clinical studies with the National Cancer Institute, American Cancer Society, and European Medicines Agency.
If your patient is interested in taking part in a clinical trial listed on clinicaltrials.gov, the Leal Health service can help them find the right trial, for free. Share this link with your patient to provide them with more information.
To learn more about rezatapopt in the PYNNACLE study, please visit clinicaltrials.gov.
Please contact the PMV Pharmaceuticals Clinical Study Information Center
+1 (609) 235-4038
clinicaltrials@pmvpharma.com
Rezatapopt is an investigational agent that has not been approved by any health authority.
Images do not depict actual trial participants.
MA-586-0107 October 2025