This study is a Phase 1, single center, open-label study, assessing single agent dose
escalation of OKI-179.
Patients must meet all of the following criteria to be eligible for enrollment.
- Histologically or cytologically confirmed solid tumors, advanced or metastatic
disease, refractory to standard therapy or for whom no standard therapy exists, or the
patient is ineligible for standard therapy(ies).
- At least 1 measurable lesion based on Response Evaluation Criteria in Solid Tumor
(RECIST) version 1.1.
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1 within 14 days
prior to Cycle 1 Day 1.
- Signed informed consent prior to initiation of any study-related procedures that are
not considered standard of care.
- Male or female, ≥ 18 years of age at time of signing consent.
- Adequate hematologic and organ function as defined by the following criteria within 14
days prior to Cycle 1 Day 1:
- Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; excluding measurements obtained within
7 days after daily administration of filgrastim/sargramostim or within 3 weeks after
administration of pegfilgrastim.
- Platelet count ≥ 100 × 109/L; excluding measurements obtained within 3 days after
transfusion of platelets.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper
limits of normal (ULN); if liver function abnormalities are due to underlying liver
metastases, AST and ALT ≤ 5 × ULN.
- Total serum bilirubin ≤ 1.5 × ULN, or ≤ 3 × ULN if attributed to Gilbert's Syndrome.
- Serum creatinine ≤ 1.5 x ULN or Creatinine clearance (CrCl) ≥ 50 mL/min; the CrCl can
be measured from urine or calculated from serum creatinine (Cockcroft‑Gault Equation).
- Female patients of childbearing potential must have a negative serum beta-human
chorionic gonadotropin (β-hCG) test within 14 days prior to Cycle 1 Day 1.
- Male patients and female patients of childbearing potential must agree to use an
effective method of contraception per institutional standard prior to the first dose
and for 90 days after the last dose of OKI-179.
- Willingness and ability to comply with all scheduled visits, treatment plan,
laboratory tests and other study procedures.
Patients meeting any of the following criteria are ineligible for enrollment in the study:
- Any of the following treatment interventions within the specified time frame prior to
Cycle 1 Day 1:
- Major surgery within 28 days (the surgical incision should be fully healed prior to
study drug administration).
- Radiation therapy within 21 days; however, if the radiation portal covered ≤ 5% of the
bone marrow reserve, the patient is eligible irrespective of the end date of
radiotherapy. None of the recently irradiated lesions can be included in the
measurable disease assessment.
- Cytotoxic therapy within 21 days (nitrosoureas or mitomycin within 42 days,
capecitabine within 14 days).
- Monoclonal antibodies within 28 days.
- Current use of an investigational agent that is not expected to be cleared by Cycle 1
Day 1 or that has demonstrated to have prolonged/late side effects.
- Continuation of luteinizing hormone-releasing hormone (LHRH) agonists for prostate
cancer, bisphosphonates for bone disease, denosumab for bone metastases and
corticosteroids are permitted provided the dose does not change during the study.
- Side effects from prior treatment interventions not resolved to a Grade ≤ 1 (except
alopecia or peripheral neuropathy).
- Prior Histone deacetylase (HDAC), pan-deacetylase (DAC), heat shock protein 90 (HSP90)
inhibitors or valproic acid for the treatment of cancer.
- Concomitant malignancies or previous malignancies with less than a 2-year disease free
interval at the time of enrollment. Patients with adequately resected basal or
squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or
Stage 1 prostate cancer or others deemed to be cured by surgery alone or surgery plus
radiotherapy in the judgment of the Investigator may enroll irrespective of the time
- Medical, psychiatric, cognitive, or other conditions that compromise the patient's
ability to understand the patient information, to give informed consent, to comply
with the study protocol, or to complete the study.
- Any severe concurrent disease or condition (including active systemic infection
requiring systemic therapy, uncontrolled diabetes mellitus, symptomatic congestive
heart failure, uncontrolled hypertension, unstable angina pectoris, or cardiac
arrhythmia) which, in the judgment of the Investigator, would make the patient
inappropriate for study participation.
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Significant gastrointestinal abnormalities, including an inability to take oral
medication, requirement for IV alimentation, active peptic ulcer, chronic diarrhea or
vomiting considered to be clinically significant in the judgment of the Investigator,
or prior surgical procedures affecting absorption.
- Known positive serology for the human immunodeficiency virus (HIV) (HIV 1/2
antibodies) or acquired immunodeficiency syndrome (AIDS)-related illness, and/or known
active hepatitis B (e.g., hepatitis B surface antigen-reactive) or hepatitis C (e.g.,
hepatitis C virus ribonucleic acid [qualitative]).
- Pregnant or lactating females.
- 12-lead electrocardiography (ECG) demonstrating a QT interval corrected for heart rate
using Fridericia's formula (QTcF) of ≥ 450 msec for males and ≥ 470 msec for females
(mean of the triplicate ECG measurements), with the exception for patients with an
atrioventricular pacemaker or other conditions (e.g., right bundle branch block) that
render the QT measurement invalid.
- History or current evidence of congenital long QT syndrome.
- Taking medications that lead to significant QT prolongation.