CVM-1118 combined with Nivolumab for advanced liver cancer

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

This study is testing if a new cancer drug called CVM-1118, when combined with Nivolumab, can help people with advanced liver cancer who haven't had success with other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 95 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: TaiRx, Inc. (Industry-sponsored)
• Drugs / interventions: atezolizumab, bevacizumab, lenvatinib, immunotherapy, nivolumab
• Locations: 5 sites (Kaohsiung City and 4 other locations)
• Trial ID: NCT05257590 on ClinicalTrials.gov

What this trial studies

This phase 2 trial investigates the efficacy of CVM-1118, a new anti-cancer drug, in combination with Nivolumab, a checkpoint inhibitor, for patients with unresectable advanced hepatocellular carcinoma. The study aims to evaluate how well this combination therapy works in promoting cancer cell death and inhibiting tumor growth, particularly in patients who have not responded to previous treatments. The safety of CVM-1118 has already been established in earlier studies, and this trial will further explore its potential benefits when paired with Nivolumab. Participants will be closely monitored for treatment effects and safety outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with unresectable advanced hepatocellular carcinoma who have progressed after prior systemic therapies.

Not a fit: Patients with resectable liver cancer or those who have not received prior systemic anti-cancer therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this combination therapy could provide a new treatment option for patients with advanced liver cancer who have limited alternatives.

How similar studies have performed: Other studies have shown promise with checkpoint inhibitors like Nivolumab in treating various cancers, suggesting potential for success with this novel combination approach.

Eligibility criteria

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

Where this trial is running

Kaohsiung City and 4 other locations

• Kaohsiung Chang Gung Memorial Hospital — Kaohsiung City, Taiwan (Recruiting)
• Keelung Chang Gung Memorial Hospital — Keelung, Taiwan (Recruiting)
• National Cheng Kung University Hospital — Tainan, Taiwan (Recruiting)
• National Taiwan University Hospital — Taipei, Taiwan (Recruiting)
• Taipei Veterans General Hospital — Taipei, Taiwan (Recruiting)

Study contacts

• Principal investigator: Pei-Jer Chen, MD/PhD — National Taiwan University Hospital
• Study coordinator: Yen-Ling Chen, PhD

Conditions Hepatocellular Carcinoma; Advanced Cancer; Oncology; Nivolumab; Hepatoma