| Eligibility |
Inclusion Criteria:
1. Age 18 years or older;
2. Patients with histologically or cytologically confirmed, unresectable advanced solid
tumors that have progressed despite standard therapy or for which no standard therapy
exists;
3. Patients must have at least one measurable lesion as defined by RECIST v1.1;
4. ECOG performance score 0 or 1;
5. Life expectancy = 3 months;
6. Patients who have sufficient Baseline organ function and whose laboratory data meet
the following criteria at enrollment:
1. Absolute neutrophil count (ANC)=1.5 × 109/L;
2. Platelets =100 × 109/L;
3. Hemoglobin =90g/dL;
4. Liver function:
Serum bilirubin =1.5 × upper limit of normal (ULN) or = 3×ULN in any subject with
Gilbert's Syndrome; Aspartate aminotransferase(AST) and alanine
aminotransferase(ALT) =2.5 × ULN without liver metastases, or =5 × ULN if the
patient has documented liver metastases;
5. International normalization ratio =1.2 if the patient is not on anticoagulants,
or =3 if the patient is on anticoagulants;
6. Serum creatinine =1.5 mg/dL, or estimated glomerular filtration rate (eGFR)=60
mL/min/1.73 m2;
7. Women of childbearing potential must have a negative serum pregnancy test prior to
study entry, and agree to use adequate contraception from study entry through at least
1 month after the last dose of study drug. A female patient of nonchildbearing
potential will have had at least 12 continuous months of natural (spontaneous)
amenorrhea, follicle stimulating hormone level =40 mIU/mL at Screening, and an
appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms),
or have had surgical bilateral oophorectomy, hysterectomy, or tubal ligation =6 weeks
prior to Screening; in the case of oophorectomy alone, reproductive status will be
confirmed by hormone level assessment;
8. A male patient must agree to use adequate contraception (male condom with spermicide
or provide evidence of successful vasectomy; sterile sexual partner; or female sexual
partner who uses an intrauterine device with spermicide, a female condom with
spermicide, a contraceptive sponge with spermicide, an intravaginal system, a double
diaphragm with spermicide, a cervical cap with spermicide) from study entry through at
least 1 month after the last dose of study drug;
9. Patients must provide written informed consent prior to any study procedures.
Exclusion Criteria:
- Disease
1. Patients with symptomatic central nervous system (CNS) metastases or
carcinomatous meningitis; Note: Patients with treated CNS metastases may
participate in this trial if the patient has completed radiotherapy or surgery
for CNS metastases >2 weeks prior to study entry and if the patient is
neurologically stable = 2 weeks (no new neurologic deficits from brain metastasis
on Screening clinical examination, no new findings on CNS imaging, and no
corticosteroids being used).
Medical Conditions
2. Patients who have a history of another primary malignancy, with the exception of
locally excised non-melanoma skin cancer and carcinoma in situ of uterine cervix.
A patient who has had no evidence of disease from another primary cancer for 3 or
more years is allowed to participate in the study;
3. Patients who have a known history of active hepatitis C or chronic hepatitis B
("active hepatitis" defined as HCV RNA level = 103 copies/mL for hepatitis C or
HBV DNA level = 104 copies/mL for hepatitis B at Screening);
4. Patients who have a known diagnosis of human immunodeficiency virus (HIV);
5. Patients who have any severe and/or uncontrolled medical conditions or other
conditions that, in the opinion of the Investigator and Sponsor, could affect the
patient's participation in the study such as:
1. Uncontrolled diabetes mellitus, HbA1c=8%;
2. Malignant illnesses that are uncontrolled or whose control may be
jeopardized by treatment with this study treatment;
3. Moderate or severe hepatic impairment, i.e., Child-Pugh class B or C (see
appendix 8.6);
4. Autoimmune disorders with systemic therapy;
6. Patients who with an allo-transplant of any kind (including those with a
xenograft heart valve);
7. Any significant ophthalmologic abnormality, including but not limited to the
following:
1. Grade 2 or greater severity syndrome of dry eye;
2. Keratoconjunctivitis sicca;
3. Sjogren's syndrome;
4. Iritis;
8. Patients who have a history of definite neurological disorders that affected
brain function activity, including epilepsy or dementia;
9. Active infections requiring antibiotic intravenous therapy at Screening;
10. Pregnancy or lactation;
11. Patients with any comorbid medical disorder that, in the opinion of the
Investigator or Sponsor, may increase the risk of toxicity; Organ Function and
Laboratory Values
12. Patients who have impaired cardiac function or clinically significant cardiac
diseases, including any of the following:
1. Baseline QT interval corrected for heart rate using Fridericia's formula
>480 msec or congenital long QT syndrome;
2. Concomitant diseases that could prolong the QT interval, as assessed by the
Investigator, such as autonomic neuropathy (caused by diabetes or
Parkinson's disease), cirrhosis, uncontrolled hypothyroidism, or grade 3 or
greater severity electrolyte abnormality (CTCAE v5.0);
3. Concomitant medications known to prolong the QT interval;
4. History or presence of serious uncontrolled ventricular arrhythmias;
5. Left ventricular ejection fraction <50% assessed by echocardiogram;
6. Any of the following within 3 months prior to the first dose of study
medication: myocardial infarction, severe/unstable angina, coronary artery
bypass graft, congestive heart failure, cerebrovascular accident, or
transient ischemic attack;
7. Other clinically significant heart disease such as congestive heart failure
NYHA Class ? or greater severity and requiring heart transplant or
uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic
blood pressure > 100 mmHg, in spite of antihypertensive medication); Prior
Therapy
13. Chemotherapy, biologic therapy, herbal therapy, radiotherapy or investigational
agents within 5 half lives or within 4 weeks (whichever is longer) prior to
administration of the first dose of study drug on Day 1 or have not recovered to
grade 1 or below from the side effects of such therapy (excluding cases of
alopecia);
14. Patients received potent CYP3A4 inducer or inhibitor within 2 weeks prior to
administration of the first dose of study drug on Day 1.
15. Patients received systemic corticosteroids within 2 weeks prior to administration
of the first dose of study drug on Day 1.
16. Major surgery for any cause within 4 weeks of first dosing;
17. Treated with immunomodulator (e.g., motolimod, GS9688, IMO4200, E-6742, E-6887,
etc).
18. Patients who have a history of allergic reactions (significant urticaria,
angioedema, anaphylaxis) attributed to compounds of similar chemical or biologic
composition to DN1508052-01; Patients with scheduled surgeries or who are, in the
Investigator's opinion, likely to require surgery.
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