Study of Narazaciclib (ON 123300) Plus Letrozole in Endometrial Cancer and Other Gynecologic Malignancies

Exclusion criteria

• . Phase 1 (Dose escalation cohorts): Cancer other than endometrial or other gynecologic malignancy.
• . Have received a cyclin-dependent kinase (CDK) 4/6 inhibitor in the past.
• . Have any significant medical condition, laboratory abnormality, or psychiatric illness that, in the opinion of the Investigator, would prevent the patient from participating in the study or present an unacceptable risk to the patient.
• . Are at risk for Torsades de pointes (TdP): Patients who have a marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval \>470 msec) using Fredericia's QT correction formula, or who have a history of additional risk factors for TdP (eg, heart failure, hypokalemia, family history of Long QT Syndrome), or who are currently taking medications that prolong the QT/QTc interval.
• . Have uncontrolled intercurrent or significant medical illness, serious underlying medical condition, abnormal laboratory finding, or psychiatric illness/social situation that might, in the Investigator's or the Sponsor's judgment, prevent the participant from receiving study treatment or being followed in this study, or otherwise renders the participant inappropriate for the study, including but not limited to ongoing or active infection, bleeding, congestive heart failure, unstable angina, cardiac arrhythmia, oxygen-dependent lung disease, and psychiatric illness/social situations that limit participation compliance with study procedures and requirements.
• . Are currently taking or within 5 half-lives of taking strong inducers and inhibitors of cytochrome P450 enzyme (CYP)2C8 and CYP3A4.
• . Have a recent history of venous thromboembolic events, defined as event occurring \<6 months prior to screening and also currently on therapy, known underlying hypercoagulability, or a major thromboembolic event within the past 2 years.
• . Have baseline Grade ≥2 diarrhea.