RecruitingPhase 2NCT05257590

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

A Phase 2, Open-Label Study of CVM-1118 in Combination With Nivolumab in Subjects With Unresectable Advanced Hepatocellular Carcinoma

Sponsor

TaiRx, Inc.

Enrollment

95 participants

Start Date

May 23, 2022

Study Type

INTERVENTIONAL

Conditions

Hepatocellular Carcinoma Advanced Cancer

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

Min Age: 18 Years

Inclusion Criteria22

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 Criteria15

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

Interventions

DRUGNivolumab Injection [Opdivo]

Nivolumab will be administered at 240 mg, IV, Q2 weeks with an option for 480 mg, IV, Q4 weeks starting with Cycle 3 if judged to be reasonable by the investigator based on the safety and tolerability.

DRUGCVM-1118

CVM-1118 will be administered 200 mg, PO, BID with an option to increase the starting dose to 300 mg, PO, BID for the subsequent subjects following assessment of safety data from the initial 10 subjects.