The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)
Sponsored by PMV Pharmaceuticals, Inc
About this study
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.
Rezatapopt is a first-in-class, oral, small molecule p53 reactivator that is selective for the TP53 Y220C mutation. The primary objective of Phase 2 Monotherapy is to evaluate the efficacy of rezatapopt at the Recommended Phase 2 Dose (RP2D) including the Overall Response Rate (ORR) in the Ovarian Cancer Cohort and the ORR across all cohorts as determined by blinded independent central review. Secondary objectives of Phase 2 are to characterize the safety, pharmacokinetic (PK) properties, quality of life, and other efficacy measures of PC14586 rezatapopt at the RP2D. Enrollment is open for the Phase 2 Monotherapy portion of the study. The primary objective of Phase 1 Monotherapy is to establish the maximum tolerated dose (MTD) and RP2D of rezatapopt. Secondary objectives are to character…
Where this study is enrolling
- Call 877-632-6789
The University of Texas MD Anderson Cancer Center
Houston, Texas
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Who can participate
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 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
- ✕Additional Criteria for Exclusion from Phase 2 (rezatapopt monotherapy)
- ✕Known KRAS mutation, defined as a single nucleotide variant (SNV) (Phase 2)
- ✕Additional Criteria for Exclusion from Phase 1b (rezatapopt) + pembrolizumab combination)
- ✕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
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Trial data sourced from ClinicalTrials.gov.