Namodenoson in the Treatment of Advanced Hepatocellular Carcinoma in Patients With Child-Pugh Class B7 Cirrhosis

Inclusion Criteria:

1. Males and females at least 18 years of age.

2. Diagnosis of HCC:

• For patients without cirrhosis at the time of diagnosis, histologicconfirmation is required (archival tissue is acceptable).

• For patients with underlying cirrhosis at the time of diagnosis, diagnosis ofHCC established according to the American Association for the Study of LiverDiseases Practice Guideline algorithm (Marrero 2018).

3. HCC is advanced (i.e., treatment-refractory or metastatic) and no standard therapiesare expected to be curative.

4. HCC has progressed on at least 1, but no more than 2, prior systemic treatmentregimens; prior locoregional therapy is allowed.

5. Barcelona Clinic Liver Cancer (BCLC) Stage B or C (Llovet 1999).

6. Prior HCC treatment was discontinued for at least 2 weeks prior to the BaselineVisit.

7. Measurable disease by RECIST v1.1 (Eisenhauer 2009).

8. ECOG PS of ≤ 1.

9. Cirrhosis classified as CPB7; if ascites is used as a scoring criterion, it must beclassified as Grade ≥2 by the Clinical Practice Guidelines of the EuropeanAssociation for the Study of the Liver (EASL 2010).

10. The following laboratory values must be documented within ten days prior to thefirst dose of study drug:

• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L

• Platelet count at least 75 × 10^9/L

• Creatinine clearance at least 50 mg/dL (estimated glomerular filtration rate bythe Cockcroft-Gault or the Modification of Diet in Renal Disease methods)

• AST and ALT ≤ 5 × the upper limit of normal (ULN)

• Total bilirubin ≤ 3.0 mg/dL

• Serum albumin ≥ 2.8 g/dL.

11. Life expectancy of ≥ 6 weeks.

12. For women of childbearing potential, negative serum pregnancy test result.

13. Provide written informed consent to participate.

14. Willing to comply with scheduled visits, treatment plans, laboratory assessments,and other trial-related procedures.

Exclusion Criteria:

1. Receipt of >2 prior systemic drug therapies for HCC.

2. Receipt of systemic cancer therapy, immunomodulatory drug therapy, immunosuppressivetherapy, or corticosteroids > 20 mg/day prednisone or equivalent within 14 daysprior to the Baseline Visit or concurrently during the trial.

3. Locoregional treatment within 4 weeks prior to the Baseline Visit.

4. Major surgery or radiation therapy within 4 weeks prior to the Baseline Visit.

5. Use of any investigational agent within 4 weeks prior to the Baseline Visit.

6. Concomitant use of P-glycoprotein (P-gp)/breast cancer resistance protein (BCRP)inhibitors and/or substrates with a narrow therapeutic index unless the medicationcan be taken at least 3 hours before or after taking the investigational product (see Section 12.2).

7. Child-Pugh Class A, B8/9, or C cirrhosis.

8. Hepatic encephalopathy.

9. Occurrence of esophageal or other gastrointestinal hemorrhage requiring transfusionwithin 4 weeks prior to the Baseline Visit.

10. Uncontrolled or clinically unstable thyroid disease, per judgment of the PrincipalInvestigator.

11. Active bacterial, viral, or fungal infection requiring systemic therapy or operativeor radiological intervention.

12. Known human immunodeficiency virus- or acquired immunodeficiency syndrome-relatedillness.

13. Liver transplant.

14. Active malignancy other than HCC.

15. Uncontrolled arterial hypertension or congestive heart failure (New York HeartAssociation Classification 3 or 4).

16. Angina, myocardial infarction, cerebrovascular accident, coronary/peripheral arterybypass graft surgery, transient ischemic attack, or pulmonary embolism within 3months prior to initiation of study drug.

17. History of, or ongoing, cardiac dysrhythmias requiring treatment, atrialfibrillation of any grade, or persistent prolongation of the QTc (Fridericia)interval to > 470 msec (patients with bundle branch block will not be excluded forQTc reasons).

18. Pregnant or lactating female.

19. Women of childbearing potential, unless they agree to use dual contraceptive methodswhich, in the opinion of the Investigator, are effective and adequate for thepatient's circumstances while on study drug.

20. Men who partner with a woman of childbearing potential, unless they agree to useeffective, dual contraceptive methods (i.e., a condom, with female partner usingoral, injectable, or barrier method) while on study drug and for 3 months afterward.

21. Any severe, acute, or chronic medical or psychiatric condition, or laboratoryabnormality that may increase the risk associated with trial participation or studydrug administration; may interfere with the informed consent process and/or withcompliance with the requirements of the trial; or may interfere with theinterpretation of trial results and, in the Investigator's opinion, would make thepatient inappropriate for entry into this trial.