MC# 21-12 - An Exploratory Phase I Study to Assess the Safety, Tolerability, and Pharmacokinetics of ON 123300 Capsules Administered Orally as Escalating Daily Doses in Patients with Advanced Cancer Relapsed or Refractory to at Least One (1) Prior Line of Therapy

  • Agent(s): ON 123300
  • Disease Type(s): Solid Tumor
  • Phase(s): I
  • Drug Classification(s): Small Molecule, Targeted Therapy
  • Molecular Target(s): CDK4/6, ARK5, NUAK1 protein
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Mechanism of Action

ON 123300 is a small molecule, dual inhibitor of CDK4/6 and ARK5, a key enzyme controlling cellular energy homeostasis.  Inhibition of ARK5 by ON 123300 collapses oncogene-altered energy metabolism, leading to programmed cell death.

Purpose

In this study, the sponsor and investigators want to learn:

  • About the safety and tolerability of ON 123300
  • If ON 123300 prevents or delays tumor growth or shrinks existing tumors
  • How much ON 123300 is absorbed into the blood and how fast it is removed
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:
    1. Hematologic:
      1. absolute neutrophil count (ANC) ≥1.0 × 109/Liter (L)
      2. platelets ≥100 × 109/L, and
      3. hemoglobin ≥8 g/deciliter (dL)
    2. Hepatic:
      1. Total bilirubin ≤1.5 times the upper limit of normal (ULN) and
      2. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 times ULN (or ALT and AST ≤5 times ULN if liver metastases are present)
    3. Renal:
      1. 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 cytochrome P450 enzyme (CYP)2C8 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)

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://clinicaltrials.gov/ct2/show/NCT04739293

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Re: MC# 21-12