Safety and Efficacy of KLS-1 Monotherapy in Malignant Neoplasms

Inclusion Criteria:

Phase I and Phase II - solid tumors cohorts

1. Adult (male or female) aged ≥18 years.

2. Signed informed consent prior to any study-specific procedures.

3. Patients who are willing to make themselves available for the duration of the studyand are willing to follow study procedures.

4. Have a performance status on the Eastern Cooperative Oncology Group (ECOG) scale of: Phase I - 0 or 1; Phase II - 0-2.

5. Have an estimated life expectancy of ≥12 weeks.

6. Have adequate organ function including:

a. Hematologic:

• ANC ≥1.5 x 109/L

• Platelets ≥100 x 109/L

• Hemoglobin ≥90 g/L b. Hepatic:

• Albumin ≥30 g/L

• Bilirubin ≤1.5 times upper limit of normal (ULN)

• ALT and AST ≤2.5 x ULN. If the liver has tumor involvement, AST and ALT ≤5 xULN are acceptable. c. Renal:

• Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 d. Bloodcoagulation:

• International Normalized Ratio (INR) or activated partial prothrombin time (aPTT) <1.5 x ULN and > 0.8 x LLN lower limit of normal (LLN).

7. Have discontinued all chemotherapy, investigational therapy, molecularly targetedtherapy, and cancer-related hormonal therapy at least 30 days prior to studyenrollment (6 weeks for mitomycin-C or nitrosoureas).

8. Have discontinued biologic therapy and immunotherapy at least 21 days prior to studyenrollment.

9. Patients who have had radiation therapy must be fully recovered in the opinion ofthe investigator prior to enrolling on study.

10. Are recovered or recovering from the acute adverse effects of any chemotherapy,biologic therapy, immunotherapy, molecularly-targeted therapy, cancer-relatedhormonal therapy, and investigational therapy (≤Grade 1 or baseline), with theexception of alopecia or Grade 2 neuropathy.

11. Have received at least 1 but no more than 4 prior systemic therapies for CLL.

12. Patients who have had surgery must be fully recovered in the opinion of theinvestigator prior to enrolling on study (but not less than 28 days for majorsurgery and 14 days for minor surgery).

13. Female patients with reproductive potential must agree to use 2 forms of highlyeffective contraception during the study and for at least 3 months following thelast dose of IMP. Sexually active male patients must use a barrier method ofcontraception (condom) during the study and for at least 3 months following the lastdose of IMP.

14. Females with child-bearing potential must have had a negative pregnancy test result ≤28 days prior to the first dose of IMP, as well as ≤1 day prior to the first doseof IMP.

15. Patients must be, in the judgment of the investigator, appropriate candidates forexperimental therapy, and no standard therapy would confer clinical benefit to thepatients.

16. Patients must have at least one lesion that is measurable by RECIST v.1.1.

Phase I 17. Patients must have histologically proven evidence of any type of metastatic solid tumor (excluding primary brain tumor) that is evaluable and for whom no approved therapy with demonstrated clinical benefit is available or patients who are intolerant or have declined standard therapy.

Phase II 18. Patients must have histologically proven evidence of a solid tumor that is locally advanced and/or metastatic and for whom no approved therapy with demonstrated clinical benefit is available or patients who are intolerant or have declined standard therapy as follows:

1. Cutaneous melanoma

2. Prostate cancer

3. Pancreatic cancer

Phase II - CLL cohort

1. Adult (male or female) aged ≥18 years.

2. Signed informed consent prior to any study-specific procedures.

3. Patients who are willing to make themselves available for the duration of the studyand are willing to follow study procedures.

4. Subjects with confirmed diagnosis of per iwCLL 2008.

5. Documented disease progression that meets at least one of the iwCLL criteria forrequiring treatment.

6. Measurable disease defined by either absolute lymphocyte count (ALC ≥ 5 x 109/L) ornodal lesion by computed tomography (CT).

7. Have a performance status on the Eastern Cooperative Oncology Group (ECOG) scale ≤

9. Have an estimated life expectancy of ≥16 weeks.

10. Have adequate organ function including:

a. Adequate hematologic function in the absence of transfusions (within 6 weeksprior to first dose of study medication) and independent of growth factor supportfor at least 7 days with the exception of pegylated G-CSF which requires at least 14days, defined as:

• WBC ≥3.0 x 109/L

• ANC ≥1.0 x 109/L

• Platelets ≥50 x 109/L or ≥ 25 × 109/L if thrombocytopenia is related to CLL b.Hepatic:

• Albumin ≥30 g/L

• Bilirubin ≤2 x ULN. Subjects with known Gilbert's Syndrome or disease-relatedhemolysis must have a total bilirubin ≤ 3 x ULN

• ALT and AST ≤2.5 x ULN. c. Renal:

• Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 d. Bloodcoagulation:

• International Normalized Ratio (INR) or activated partial prothrombin time (aPTT) <1.5 x ULN and > 0.8 x LLN.

10. Have discontinued all chemotherapy, immunotherapy, investigational therapy, biologictherapy, molecularly targeted therapy, and cancer-related hormonal therapy at least 30 days prior to study enrollment (6 weeks for mitomycin-C or nitrosoureas).

11. Are recovered or recovering from the acute adverse effects of any chemotherapy,biologic therapy, immunotherapy, molecularly targeted therapy, cancer-relatedhormonal therapy, and investigational therapy (≤Grade 1 or baseline), with theexception of alopecia or Grade 2 neuropathy.

12. The subject must also agree to pretreatment and on-treatment bone marrow aspirates.

13. Have received at least 1, but not more than 3 prior lines of therapy according tocurrent guidelines.

14. Patients who have had surgery must be fully recovered in the opinion of theinvestigator prior to enrolling on study (but not less than 28 days for majorsurgery and 14 days for minor surgery).

15. Female patients with reproductive potential must agree to use 2 forms of highlyeffective contraception during the study and for at least 3 months following thelast dose of IMP. Sexually active male patients must use a barrier method ofcontraception (condom) during the study and for at least 3 months following the lastdose of IMP.

16. Females with child-bearing potential must have had a negative pregnancy test result ≤28 days prior to the first dose of IMP, as well as ≤1 day prior to the first doseof IMP.

17. Patients must be, in the judgment of the investigator, appropriate candidates forexperimental therapy, and no standard therapy would confer clinical benefit to thepatients.

Exclusion Criteria:

1. Have another tumor of another location except basal cell carcinoma.

2. Have a history of organ transplant (e.g., heart, lungs, liver, bone marrow, orkidney).

3. Females who are pregnant or breastfeeding.

4. Have symptomatic human immunodeficiency virus (HIV) infection, known HIV positivetest results or have chronic active hepatitis B or C (screening is not required).

5. Positive COVID-19 test or signs of coronavirus infections.

6. Have clinically significant cardiac disease including any of the following:

• A history of congenital long QT syndrome, symptomatic bradycardia, ventriculararrhythmia, uncontrolled atrial fibrillation, second- or third-degree heartblock, or other conduction abnormality that in the opinion of the investigatorwould preclude safe participation in this study.

• Congestive heart failure (New York Heart Association Class ≥3).

• Unstable angina pectoris, acute myocardial infarction, or stroke ≤12 monthsprior to enrollment.

• QTcF prolongation >450 msec.

7. Currently taking medication known to prolong the QT interval or induce TdP, whichcannot be discontinued or substituted.

8. Uncontrolled type 1 or 2 diabetes with high risk of hypoglycemia.

9. Are a family member of the investigator or staff of the study site.

10. Are currently enrolled in another interventional clinical study of aninvestigational therapy.

11. Hypersensitivity to any components of KLS-1. Additional exclusion criterion forpatients enrolled in Phase II to CLL cohort

12. History of Richter's transformation or prolymphocytic leukemia.