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

Summary

CVM-1118 is a new small molecule chemical entity being developed as a potential anti-cancer therapeutic by TaiRx, Inc. CVM-1118 is a potent anti-cancer agent in numerous human cancer cell lines. The safety of administrating CVM-1118 on human has been evaluated from the phase 1 study. The objective of the phase 2 study is to further investigate the efficacy of CVM-1118 with nivolumab for subjects with unresectable advanced hepatoma.

Eligibility

Inclusion Criteria:

* 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.

Exclusion Criteria:

* HCC with portal vein invasion at the main portal branch (Vp4)
* Known history of esophageal varices or gastrointestinal bleeding within the past 3 months
* 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 days prior 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 oral medications
* Psychiatric illness or social situation that would interfere with compliance with study requirements
* History of clinically significant cardiovascular abnormalities

Conditions5

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