CVM-1118 in Combination With Nivolumab for Unresectable Advanced Hepatocellular Carcinoma

Inclusion Criteria:

• Age 18+ (20+ for subjects in Taiwan)

• Diagnosis of hepatocellular carcinoma

• Pathologically or cytologically-confirmed or clinically diagnosed in accordancewith American Association for the Study of Liver Diseases (AASLD) criteria (i.e., radiologic imaging with cross-sectional multiphasic contrast CT or MRIshowing a ≥ 1 cm liver lesion)

• Subjects with advanced-stage, unresectable hepatocellular carcinoma that is notappropriate for potentially curable therapy who have progressed from, beenintolerant of prior systemic anti-cancer therapies (e.g., sorafenib, lenvatinib,atezolizumab in combination with bevacizumab).

• Barcelona Clinic Liver Cancer (BCLC) stage B not appropriate for or with diseaseprogression after local regional therapy, or BCLC stage C

• Child-Pugh liver function class A

• Measurable disease (per mRECIST)

• ECOG performance status of 0 to 1

• Adequate laboratory parameters including:

• AST and ALT ≤ 3.0 x ULN (≤ 5.0 x ULN if due to liver involvement)

• Total serum bilirubin ≤ 2.0 x ULN (≤ 3.0 x ULN for subjects with documentedGilbert's syndrome)

• ANC ≥1500/µL

• Platelets ≥ 90,000/µL

• HGB ≥ 9.0 g/dL

• Serum creatinine clearance of ≥ 50 mL/min based on Cockcroft-Gault formula

• Serum albumin ≥ 2.8 gm/dL

• INR ≤ 2.3

• PT/aPTT ≤ 1.2 x ULN

• QTcF ≤ 480 msec

• Subjects are eligible to enroll if they have HBV-, or HCV-HCC, defined as follows:

• Chronic HBV infection as evidenced by detectable HBV DNA or HBsAg. Subjectswith chronic HBV infection must be on antiviral therapy and have HBV DNA <500IU/mL. If not on an antiviral therapy at screening, then subjects must bewilling to start the antiviral therapy at the time of consent.

• Active or resolved HCV infection as evidenced by detectable HCV RNA orantibody.

Exclusion Criteria:

• HCC with portal vein invasion at the main portal branch (Vp4)

• Known history of esophageal varices or gastrointestinal bleeding within the past 3months

• Prior immunotherapy for hepatoma

• ≤ 7 days from prior limited field palliative irradiation therapy and C1D1

• ≤ 28 days from prior irradiation therapy and C1D1

• ≤ 14 days (or 5 half-lives) from prior systemic anticancer therapy and C1D1

• ≤ 28 days from local regional therapy (e.g., trans-arterial embolization,radiofrequency ablation) and C1D1

• Presence of other active cancer(s) likely to require treatment in the next two (2)years or likely to impact the assessment of any study endpoints

• Active bacterial or fungal infection(s) requiring systemic therapy within 7 daysprior to C1D1

• Known CNS metastases

• Known history of HIV infection

• Females who are currently pregnant or breast-feeding

• Known gastrointestinal disease that may significantly alter the absorption of oralmedications

• Psychiatric illness or social situation that would interfere with compliance withstudy requirements

• History of clinically significant cardiovascular abnormalities