LIONS (PLK4 Inhibitor in Advanced Solid Tumors)

Inclusion Criteria:

• Written informed consent or assent, according to local guidelines, signed and datedby the patient or legal guardian prior to the performance of any study-specificprocedures, sampling, or analyses.

• Male or female and ≥ 12 years-of-age at the time of signature of the consent orassent, and are at least 6th grade reading level to consent; participants < 18 yearsof age must weigh at least 40 kg.

• Life expectancy ≥ 4 months.

• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.

• Locally advanced or metastatic solid tumor that has progressed or was nonresponsiveor intolerant to available therapies and for which no standard or available curativetherapy exists.

• Measurable disease as per RECIST v1.1 or INRC.

• Existing biomarker profile (tumor tissue or plasma) reported from a local testobtained in a CLIA-certified or equivalent laboratory demonstrating eligible tumorbiomarkers.

• Available tumor tissue.

• Molecularly eligible tumor profile from a CLIA-certified pathology report.

• Ability to comply with the protocol and study procedures detailed in the Schedule ofAssessments.

• Ability to swallow and retain oral medications.

• Acceptable organ function at screening.

• Acceptable blood counts at screening.

• Negative pregnancy test (serum or urine) for females of childbearing potential atScreening and while on study drug.

• Resolution of all toxicities of prior treatment or surgery.

• Use of highly effective forms of contraception.

Exclusion Criteria:

• History or current condition (such as transfusion dependent anemia orthrombocytopenia), therapy, or laboratory abnormality that might confound the studyresults, or interfere with the patient's participation for the full duration of thestudy treatment.

• Life-threatening illness, medical condition, active uncontrolled infection, or organsystem dysfunction or other reasons which, in the investigator's opinion, couldcompromise the patient's safety.

• Uncontrolled, symptomatic brain metastases.

• Presence of other known second malignancy with the exception of any cancer that hasbeen in complete remission for ≥ 2 years or completely resected squamous and basalcell carcinomas of the skin.

• Patients with active, uncontrolled bacterial, fungal, or viral infection, includinghepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.

• Clinically significant vascular (both arterial and venous) and non-vascular cardiacconditions, active or within 6 months prior to enrollment.

• Moderate or severe hepatic impairment (ie, Child-Pugh class B or C).

• Uncontrolled high blood pressure.

• Chemotherapy, small molecule or biologic antineoplastic agent given within 21 days.

• Previously prescribed receptor activator of nuclear factor kappa B ligand (RANKL)inhibitor initiated less than 4 months prior to trial entry. Bisphosphonates areallowed if initiated/administered at least 28 days prior to enrollment.

• I-131 Meta-Iodo-Benzyl-Guanidine (MIGB) therapy within 6 weeks prior to initiationof trial treatment.

• Prior treatment with a PLK4 inhibitor.

• Current treatment with medications that are known to prolong the QT interval.