Inclusion Criteria:

          1. ≥ 18 years of age the time of signing the informed consent form (ICF);

          2. Histological or cytological evidence of advanced and/or metastatic cancer,

               1. For Dose Escalation Cohorts, patients with measurable or non-measurable disease;

               2. For RP2D Expansion Cohort, patients with measurable disease;

          3. Patients must have received and failed at least one prior approved treatment, or have
             no therapeutic options available as deemed appropriate by their treating physician;

          4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of < 2;

          5. Life expectancy of > 3 months;

          6. Patients must be able to swallow oral capsules;

          7. Women of child-bearing potential must have a negative serum screening for pregnancy
             within 14 days prior to screening. Women and men of child-bearing potential must agree
             to use highly effective methods of birth control before entry and throughout the
             study, for up to 12 weeks following the last dose of ON 123300.

          8. Patients must understand and voluntarily sign an ICF prior to any study-related
             assessments/procedures being conducted;

          9. Patients must have the ability to understand the nature of the study and any hazards
             of participating in the study and communicate satisfactorily with the investigator to
             participate in the study.

         10. Patients must be willing and able to adhere and comply to the requirements of the
             entire study including study visit schedule and other protocol requirements;

         11. Have adequate organ function, including:

             a. Hematologic: i. absolute neutrophil count (ANC) ≥1.0 × 109/Liter (L) ii. platelets
             ≥100 × 109/L, and iii. hemoglobin ≥8 g/deciliter (dL). b. Hepatic: i. Total bilirubin
             ≤1.5 times the upper limit of normal (ULN) and ii. alanine aminotransferase (ALT) and
             aspartate aminotransferase (AST) ≤3.0 times ULN (or ALT and AST ≤5 times ULN if liver
             metastases are present).

             c. Renal: i. Serum creatinine ≤1.5 times ULN. or estimated creatinine clearance
             (calculated according to normal institutional practice) greater than 50 ml/min.

        Exclusion Criteria:

          1. Patients that have any significant medical condition, laboratory abnormality, or
             psychiatric illness that would prevent the patient from participating in the study or
             present an unacceptable risk to the patient;

          2. Patients at risk for Torsades de pointes (TdP):

               1. Who have a marked baseline prolongation of QT/QTc interval (e.g., repeated
                  demonstration of a QTc interval >480 milliseconds (ms) (CTCAE grade 1) using
                  Fredericia's QT correction formula, or

               2. who have a history of additional risk factors for TdP (e.g., heart failure,
                  hypokalemia, family history of Long QT Syndrome), or

               3. who are currently taking medications that prolong the QT/QTc interval;

          3. Patients with a diagnosis of hematological malignancies except for non-Hodgkin's
             lymphoma;

          4. Have received recent chemotherapy, hormonal therapy, other targeted cancer treatment,
             or investigational therapy within 14 days of planned first dose;

          5. Patients currently taking or within 5 half-lives of taking strong inducers and
             inhibitors of CYP2C8 and CYP3A4;

          6. History of allergic reaction attributed to compounds of similar chemical or biologic
             composition/structure to ON 123300 (e.g. prior CDK4/6 inhibitors);

          7. Uncontrolled intercurrent illness including but not limited to ongoing or active
             infection, bleeding, congestive heart failure, unstable angina, cardiac arrhythmia,
             oxygen-dependent lung disease, psychiatric illness/social situations that limit
             participation compliance with study procedures and requirements;

          8. Patients with a recent history of venous thromboembolic events, defined as event
             occurring ≤ 6 months prior to screening and also currently on therapy;

          9. Patients with baseline Grade ≥ 2 diarrhea;

         10. Patients with Grade ≥ 3 hypercalcemia (Corrected serum calcium > 12.5 mg/dL);

         11. Pregnant or nursing mothers;

         12. Have had major surgery within 14 days prior to screening to allow for post-operative
             healing of the surgical wound and site(s).

         13. Have received recent (within 28 days prior to screening) live attenuated vaccines.

         14. Have active bacterial, fungal or detectable viral infection (e.g. Human
             Immunodeficiency Virus or Hepatitis B or Hepatitis C).