Study objectives
PYNNACLE aims 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 Phase 1 portion of this study aims to find a suitable dose of rezatapopt, as well as assessing pharmacokinetics, safety and efficacy. This portion of the study is ongoing and not enrolling at this time.
The Phase 1b portion of the study aims to find a suitable dose of rezatapopt in combination with pembrolizumab, as well as assessing pharmacokinetics, safety and efficacy. This portion of the study is currently enrolling.
The Phase 2 portion of the study aims 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 all portions of the study unless otherwise specified. For full eligibility criteria, please visit clinicaltrials.gov.
Inclusion criteria:
Patients with a locally advanced or metastatic solid tumor that harbors a TP53 Y220C mutation
Patients ≥18 years (all global sites) and 12–17 years, if weight is ≥40 kg (90 lbs; Australia, South Korea and US only)
Previously treated with one or more lines of anticancer therapy
Eastern Cooperative Oncology Group performance status score* of 0 or 1
Additional criteria for the combination study (Phase 1b):
- Patients with progression of disease after one or more lines of therapy of anticancer therapy
- Measurable disease
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, including unstable angina, uncontrolled hypertension, heart attack within 6 months of screening, heart failure, and rhythm abnormalities
Additional criterion for the monotherapy study (Phase 2): Known KRAS mutation, defined as a single nucleotide variant
*The Eastern Cooperative Oncology Group performance status score is a measurement of how well a person can function and take care of themselves.1
Reference: 1. VeryWellHealth. What is Performance Status? Accessed January 2024.
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
Learn more about clinical studies with the National Cancer Institute, American Cancer Society, and European Medicines Agency.
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To learn more about rezatapopt (also known as PC14586) in the PYNNACLE study, please visit clinicaltrials.gov.
Please contact the PMV Pharmaceuticals Clinical Study Information Center
+1 (609) 235-4038
clinicaltrials@pmvpharma.com
Medical Information Request Form
For healthcare providers as well as patients and their caregivers to query PMV Pharmaceuticals for additional Medical Information.
Click here or scan the QR code for the Medical Information Request Form
Rezatapopt is an investigational agent that has not been approved by the US FDA, EMA or any other regulatory agency for the treatment of cancer.
MA-586-0014 February 2024