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

Prior treatment

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

Other illness

• Known history of esophageal varices or gastrointestinal bleeding within the past 3 months
• 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
• Known history of HIV infection
• Known gastrointestinal disease that may significantly alter the absorption of oral medications
• Psychiatric illness or social situation that would interfere with compliance with study requirements
• History of clinically significant cardiovascular abnormalities

Other

• HCC with portal vein invasion at the main portal branch (Vp4)
• Known CNS metastases
• Females who are currently pregnant or breast-feeding

• Age 18+ (20+ for subjects in Taiwan)
• Diagnosis of hepatocellular carcinoma
  • Pathologically or cytologically-confirmed or clinically diagnosed in accordance with American Association for the Study of Liver Diseases (AASLD) criteria (i.e., radiologic imaging with cross-sectional multiphasic contrast CT or MRI showing a ≥ 1 cm liver lesion)
• Subjects with advanced-stage, unresectable hepatocellular carcinoma that is not appropriate for potentially curable therapy who have progressed from, been intolerant 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 disease progression 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 documented Gilbert'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. Subjects with chronic HBV infection must be on antiviral therapy and have HBV DNA \<500 IU/mL. If not on an antiviral therapy at screening, then subjects must be willing to start the antiviral therapy at the time of consent.
  • Active or resolved HCV infection as evidenced by detectable HCV RNA or antibody.