A Study to Evaluate the Safety, Tolerability of DN1508052-01 in Advanced Solid Tumors

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 Ⅱ 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.