Clinical Study of Safety and Tolerability of CBLB502 as a Neo-adjuvant Treatment in Patients With Colorectal Cancer

Randomized Single-blind Placebo-controlled Clinical Study of Safety and Tolerability of CBLB502 as a Neo-adjuvant Treatment in Patients With Colorectal Cancer, With Different Doses and Regimens

Randomized Single-blind Placebo-controlled Clinical Study of Safety and Tolerability of CBLB502 as a Neo-adjuvant Treatment in Patients With Colorectal Cancer, With Different Doses and Regimens

Inclusion Criteria:

1. Written Patient Informed Consent for participation in the study

2. Men and women in the age above 18 years

3. Patients with confirmed diagnosis of colorectal cancer, indication to scheduled surgery for primary tumor removal

4. Should not have any previous anticancer therapy

5. Patient's life expectancy more than 3 months

6. ECOG performance status 0-1

7. Adequate hepatic and renal function:

   • Total bilirubin ≤1.5 upper limit of normal (ULN)),
   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN, regardless of the presence of liver metastases,
   • Creatinine ≤2 x ULN

8. Adequate cardiac function including:

   • LVEF ≥45 by echocardiogram (ECHO) or multi gated acquisition scan,
   • 12-lead electrocardiogram (ECG) with normal tracing or non-clinically significant changes that do not require medical intervention,
   • QTcB interval QT (QTc by Bazett's formula) < 470 msec and no history of Torsades des Pointes or other symptomatic QTcB abnormality,
   • Absence of orthostatic hypotonia

9. Negative testing for serological markers of HIV-infection, viral hepatitis В and С, syphilis

10. Content to use barrier contraception methods by male/female patient and his/her partner in the study period

Exclusion Criteria:

1. Inability to obtain written Informеd consent for participation in the study

2. History of cardiovascular abnormalities including any conditions stated below:

   • Myocardial infarction/stroke for the last 6 months,

   • Stable abnormalities in regional contractility,

   • Cardiac failure (NYHA functional class III-IV),

   • Confirmed cardiomyopathy,

   • Clinically significant arrhythmias including any conditions stated below:

     • QT prolongation syndrome,
     • History of II or III-degree AV-block,
     • Bradycardia (HR < 50 beats per min.) or tachycardia (HR >100 beats per min.)

   • Blood pressure abnormalities:

     • 2 degree uncontrolled arterial hypertension (systolic blood pressure > 160 mm Hg or diastolic blood pressure > 105 mm Hg),
     • Hypotension (systolic blood pressure < 90 mm Hg)

3. History of severe allergic, systemic and other oncologic diseases

4. Decompensated diabetes mellitus with glycolated hemoglobin level (HbA1c) > 7%

5. Administration of drug products with evident effect on immune system for previous 3 months prior screening (including corticosteroids. Remark: Topical agents (e.g. for rash treatment), inhalation aerosols (e.g. for treatment of broncho-obstructive diseases), eye drops and agents for local administration (e.g. to joint cavity) is allowed

6. Participation in other clinical studies or administration of study products for 30 days prior screening, or persisting adverse reactions of the study product

7. Patients that have not taken CBLB502

8. Patients with hypersensitivity/allergy to CBLB502 or excipients of the drug product; NSAID (including ibuprofen)

9. Pregnant or lactating women

10. History of salmonellosis

11. Body mass > 88 kg; no obesity which means BMI in the range 18.5-25 kg/m2 for women and 22-27 kg/m2 for men

12. Men and women of childbearing age which do agree to use double contraception method, oral contraception or abstain from sex contacts throughout the study

13. Alcohol abuse, drug abuse and any other medical, psychological and social reasons which may, in accordance with the investigator, affect patient's participation in the study, may prevent adequate assessment of the study results

14. Any conditions which are unstable or may endanger patient's safety and/or affect his/her adherence to the investigator instruction

15. Any patient is not able or willing to cooperate with the investigator