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

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