This study will assess the safety and tolerability of multiple dose levels of PC14586 in participants with advanced solid tumors containing a p53 Y220C mutation.

NCT04585750

Conditions

1. Advanced Solid Tumor
2. Advanced Malignant Neoplasm
3. Metastatic Cancer
4. Metastatic Solid Tumor

Interventions

1. Drug: PC14586

MeSH:Neoplasms

HPO:Neoplasm

A Phase 1/2 Open-label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of PC14586 in Patients With Advanced Solid Tumors Harboring a p53 Y220C Mutation. --- Y220C ---

This Study Will Evaluate PC14586 in Patients With Advanced Solid Tumors Harboring a p53 Y220C Mutation This study will assess the safety and tolerability of multiple dose levels of PC14586 in participants with advanced solid tumors containing a p53 Y220C mutation. --- Y220C ---

This Study Will Evaluate PC14586 in Patients With Advanced Solid Tumors Harboring a p53 Y220C Mutation This study will assess the safety and tolerability of multiple dose levels of PC14586 in participants with advanced solid tumors containing a p53 Y220C mutation. --- Y220C --- --- Y220C ---

Inclusion Criteria: - At least 18 years of age or 12 to 17 years of age after adequate adult safety data become available - Advanced solid malignancy with a p53 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 Exclusion Criteria: - Anti-cancer therapy within 21 days (or 5 half-lives) of receiving the study drug - Radiotherapy within 28 days of receiving the study drug - Primary CNS tumor - History of leptomeningeal disease or spinal cord compression - Brain metastases, unless asymptomatic and not requiring steroids for at least 2 weeks prior to receiving the study drug - Stroke or transient ischemic attack within 6 months prior to screening - Heart conditions such as unstable angina, uncontrolled hypertension, a heart attack within 6 months prior to screening, congestive heart failure, prolongation of QT interval, or other rhythm abnormalities - Strong CYP3A4 inhibitors or inducers, medications with a known risk of QT/QTc prolongation, or proton pump inhibitors - 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 Inclusion Criteria: - At least 18 years of age or 12 to 17 years of age after adequate adult safety data become available - Advanced solid malignancy with a p53 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 Exclusion Criteria: - Anti-cancer therapy within 21 days (or 5 half-lives) of receiving the study drug - Radiotherapy within 28 days of receiving the study drug - Primary CNS tumor - History of leptomeningeal disease or spinal cord compression - Brain metastases, unless asymptomatic and not requiring steroids for at least 2 weeks prior to receiving the study drug - Stroke or transient ischemic attack within 6 months prior to screening - Heart conditions such as unstable angina, uncontrolled hypertension, a heart attack within 6 months prior to screening, congestive heart failure, prolongation of QT interval, or other rhythm abnormalities - Strong CYP3A4 inhibitors or inducers, medications with a known risk of QT/QTc prolongation, or proton pump inhibitors - 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 Advanced Solid Tumor Advanced Malignant Neoplasm Metastatic Cancer Metastatic Solid Tumor Neoplasms PC14586 is a first-in-class, oral, small molecule p53 reactivator that is selective for the p53 Y220C mutation. --- Y220C ---

Inclusion Criteria: - At least 18 years of age or 12 to 17 years of age after adequate adult safety data become available - Advanced solid malignancy with a p53 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 Exclusion Criteria: - Anti-cancer therapy within 21 days (or 5 half-lives) of receiving the study drug - Radiotherapy within 28 days of receiving the study drug - Primary CNS tumor - History of leptomeningeal disease or spinal cord compression - Brain metastases, unless asymptomatic and not requiring steroids for at least 2 weeks prior to receiving the study drug - Stroke or transient ischemic attack within 6 months prior to screening - Heart conditions such as unstable angina, uncontrolled hypertension, a heart attack within 6 months prior to screening, congestive heart failure, prolongation of QT interval, or other rhythm abnormalities - Strong CYP3A4 inhibitors or inducers, medications with a known risk of QT/QTc prolongation, or proton pump inhibitors - 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 Inclusion Criteria: - At least 18 years of age or 12 to 17 years of age after adequate adult safety data become available - Advanced solid malignancy with a p53 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 Exclusion Criteria: - Anti-cancer therapy within 21 days (or 5 half-lives) of receiving the study drug - Radiotherapy within 28 days of receiving the study drug - Primary CNS tumor - History of leptomeningeal disease or spinal cord compression - Brain metastases, unless asymptomatic and not requiring steroids for at least 2 weeks prior to receiving the study drug - Stroke or transient ischemic attack within 6 months prior to screening - Heart conditions such as unstable angina, uncontrolled hypertension, a heart attack within 6 months prior to screening, congestive heart failure, prolongation of QT interval, or other rhythm abnormalities - Strong CYP3A4 inhibitors or inducers, medications with a known risk of QT/QTc prolongation, or proton pump inhibitors - 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 Advanced Solid Tumor Advanced Malignant Neoplasm Metastatic Cancer Metastatic Solid Tumor Neoplasms PC14586 is a first-in-class, oral, small molecule p53 reactivator that is selective for the p53 Y220C mutation. --- Y220C --- --- Y220C ---

Inclusion Criteria: - At least 18 years of age or 12 to 17 years of age after adequate adult safety data become available - Advanced solid malignancy with a p53 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 Exclusion Criteria: - Anti-cancer therapy within 21 days (or 5 half-lives) of receiving the study drug - Radiotherapy within 28 days of receiving the study drug - Primary CNS tumor - History of leptomeningeal disease or spinal cord compression - Brain metastases, unless asymptomatic and not requiring steroids for at least 2 weeks prior to receiving the study drug - Stroke or transient ischemic attack within 6 months prior to screening - Heart conditions such as unstable angina, uncontrolled hypertension, a heart attack within 6 months prior to screening, congestive heart failure, prolongation of QT interval, or other rhythm abnormalities - Strong CYP3A4 inhibitors or inducers, medications with a known risk of QT/QTc prolongation, or proton pump inhibitors - 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 Inclusion Criteria: - At least 18 years of age or 12 to 17 years of age after adequate adult safety data become available - Advanced solid malignancy with a p53 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 Exclusion Criteria: - Anti-cancer therapy within 21 days (or 5 half-lives) of receiving the study drug - Radiotherapy within 28 days of receiving the study drug - Primary CNS tumor - History of leptomeningeal disease or spinal cord compression - Brain metastases, unless asymptomatic and not requiring steroids for at least 2 weeks prior to receiving the study drug - Stroke or transient ischemic attack within 6 months prior to screening - Heart conditions such as unstable angina, uncontrolled hypertension, a heart attack within 6 months prior to screening, congestive heart failure, prolongation of QT interval, or other rhythm abnormalities - Strong CYP3A4 inhibitors or inducers, medications with a known risk of QT/QTc prolongation, or proton pump inhibitors - 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 Advanced Solid Tumor Advanced Malignant Neoplasm Metastatic Cancer Metastatic Solid Tumor Neoplasms PC14586 is a first-in-class, oral, small molecule p53 reactivator that is selective for the p53 Y220C mutation. --- Y220C --- --- Y220C --- --- Y220C ---

The primary objective of Phase 1 is to establish the maximum tolerated dose / recommended dose of PC14586 to treat participants with advanced solid tumors harboring a p53 Y220C mutation. --- Y220C ---

The primary objective of Phase 2 is to assess the ORR in participants with advanced solid tumors harboring a p53 Y220C mutation as determined by an independent radiology committee. --- Y220C ---