CVM-1118 plus sintilimab infusions and TACE for incurable non-metastatic liver cancer

A Phase IIa, Single-arm, Open-label Clinical Study to Evaluate the Efficacy, Safety and Pharmacokinetic (PK) of CVM-1118 in Combination With Sintilimab and Transarterial Chemoembolization (TACE) in Participants With Incurable/Non-metastatic Hepatocellular Carcinoma

This trial will test whether combining oral CVM-1118 with sintilimab infusions and TACE helps people with incurable, non-metastatic hepatocellular carcinoma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: TaiRx, Inc. (Industry-sponsored)
• Drugs / interventions: Sintilimab, radiation, prednisone
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07521852 on ClinicalTrials.gov

What this trial studies

This single-arm, open-label Phase IIa study plans to enroll about 40 adults with non-metastatic, incurable hepatocellular carcinoma who are eligible for TACE. Participants will take CVM-1118 200 mg orally twice daily and receive sintilimab 200 mg IV every three weeks, with TACE (cTACE or DEB-TACE) performed per investigator discretion. Treatment cycles last 21 days, CVM-1118 is held from 2 days before to 7 days after each TACE, and therapy continues until unacceptable toxicity, progression, withdrawal, two years, or study termination. The study is conducted at Zhongshan Hospital, Fudan University in Shanghai and the data are intended to support a future U.S. marketing application.

Who should consider this trial

Good fit: Adults (≥18) with confirmed HCC that is not amenable to curative surgery or transplant, without extrahepatic disease, Child-Pugh A liver function, at least one measurable lesion, and disease suitable for up to four TACE procedures.

Not a fit: Patients with extrahepatic/metastatic disease, impaired liver function (Child-Pugh B or C), or those who are candidates for curative resection or transplant are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this combination could improve local tumor control and delay disease progression compared with TACE alone.

How similar studies have performed: Early studies combining PD-1 inhibitors with TACE have shown promising signals, but combining TACE and sintilimab with CVM-1118 is a novel approach with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

* 1\) Participant is ≥18 years of age, at the time of providing the documented informed consent.

  2\) 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 computed tomography \[CT\] or magnetic resonance imaging \[MRI\] showing a ≥ 1 cm liver lesion).

    3\) No evidence of extrahepatic disease on any available imaging. 4) Disease not amenable to curative surgery or transplantation or curative ablation.

    5\) Disease must be amenable to TACE and anticipated to require no more than 4 TACE treatments for local disease sites, with a maximum of 2 TACE treatments per individual lesion .

    6\) Child-Pugh liver function class A (see Appendix 2). 7) At least one measurable (per RECIST 1.1) lesion (see Appendix 1). 8) Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (see Appendix 3).

    9\) Patients with hepatitis B virus (HBV) infection, defined as hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (anti-HBcAb) positive, and HBV DNA detected positive (≥10 IU/ml or above the local laboratory's standard detection limit), who have stable disease or show antiviral response (e.g., reduction in HBV DNA levels) after treatment, and agree to receive treatment during the trial, shall be allowed to enroll.

    10\) Patients with hepatitis C virus (HCV) infection who agree to receive treatment during the trial are eligible for enrollment.

    11\) Participants must have adequate organ and bone marrow function, meeting the following laboratory criteria:
  * Hematology: Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L; Platelet count (PLT) ≥75 × 10⁹/L; Hemoglobin (HGB) ≥9.0 g/dL without transfusion or erythropoietin (EPO) dependency
  * Liver Function: Total bilirubin (T-Bil) ≤2 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 × ULN; Serum albumin ≥30 g/L
  * Renal Function: Non-indexed eGFR ≥ 60 mL/min (formula in Appendix 4)
  * Coagulation: International normalized ratio (INR) ≤2 × ULN; prothrombin time (PT) ≤1.5 × ULN 12) Life expectancy of ≥12 weeks. 13) Male and female participants of childbearing potential must agree to use effective contraception from the signing of the informed consent form (ICF) until 6 months after the last dose of the investigational product. Female participants of childbearing potential are defined as premenopausal women. A negative pregnancy test result must be confirmed for all female of childbearing potential within ≤7 days prior to the first dose of the investigational product.

    14\) Signed written informed consent form and ability to comply with protocol-specified visits and related procedures.

Exclusion Criteria:

* 1\) Known hypersensitivity to CVM-1118, Sintilimab components, or severe allergic reactions to monoclonal antibodies.

  2\) Histologically/cytologically confirmed components of fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, etc.

  3\) Has HCC lesions occupying ≥50% of the liver volume. 4) Major portal vein tumor thrombosis involving the main trunk and its first-order branches (i.e., Vp3 and Vp4), as demonstrated by imaging performed during the screening period.

  5\) Is currently a candidate for liver transplantation. 6) Receipt of anti- programmed cell death protein 1 (PD-1), anti- programmed death - ligand 1 (PD-L1), or anti - programmed death - ligand 2 (PD-L2) agent or an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., Cytotoxic T - lymphocyte - associated protein 4 \[CTLA-4\]).

  7\) Receipt of locoregional therapy to existing liver lesions (such as TACE, transcatheter arterial embolization \[TAE\], transarterial radioembolization (TARE), hepatic arterial infusion, or radiation,) for treatment of HCC. Use of TACE or TAE as part of a curative therapy (e.g., in conjunction with ablation or surgery) can be acceptable if it is used in the lesions where curative therapy was attempted. However, TACE or TAE cannot have been used as sole modalities in prior curative therapy.

  8\) Receipt of prior systemic anticancer therapies for HCC. 9) History of abdominal fistula or gastrointestinal (GI) perforation, non-healed gastric ulcer that is refractory to treatment, or active GI bleeding within 6 months prior to enrollment.

  10\) Has bleeding or thrombotic disorders or is using anticoagulants requiring therapeutic INR monitoring, e.g., warfarin or similar agents. Treatment with antiplatelet agents and low molecular weight heparin is permitted.

  11\) Has clinically apparent ascites on physical examination that is not controlled with medication.

Note: Ascites detectable on imaging studies only are allowed 12) Has had clinically diagnosed hepatic encephalopathy in the last 6 months unresponsive to therapy. Participants on rifaximin or lactulose during screening to control their hepatic encephalopathy are excluded.

13\) Has medical contraindications that preclude all forms of contrast enhanced imaging (CT or MRI).

14\) Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of CVM-1118.

15\) Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula.

16\) Has clinically significant hemoptysis from any source or tumor bleeding within 2 weeks prior to the first dose of investigational product.

17\) Has significant cardiovascular impairment within 12 months of the first dose of investigational product such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II (Appendix 5), unstable angina, myocardial infarction or cerebrovascular accident stroke, or cardiac arrhythmia associated with hemodynamic instability.

18\) Has had major surgery to the liver within 4 weeks prior to the first dose of investigational product.

Note: If participant underwent major surgery, they must have adequately recovered from the toxicity and/or complications from the intervention prior to starting investigational product.

19\) Has had a minor surgery within 7 days prior to the first dose of investigational product.

20\) Has serious nonhealing wound, ulcer, or bone fracture. 21) Has received a live vaccine within 30 days prior to the first dose of investigational product.

22\) Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of investigational product.

Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks or 5 half-lives (whichever is longer) after the last dose of the previous investigational agent.

23\) Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of investigational product.

24\) Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy \[e.g., ≤10 mg prednisone\] for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is permitted.

25\) Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.

Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.

26\) Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.

27\) Patients with co-existing active HBV and HCV infections. 28) Has an active infection including tuberculosis or human immunodeficiency virus (positive HIV antibodies).

29\) Participants with proteinuria \>1+ on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein ≥1 g/24 hours will be ineligible.

30\) Has had an allogenic tissue/solid organ transplant. 31) Other conditions that, in the investigator's judgment, would increase study risk, interfere with results, or render the participant ineligible.

Where this trial is running

Shanghai, Shanghai Municipality

• Zhongshan Hospital, Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Chun-Man Chen

Conditions HCC - Hepatocellular Carcinoma; Oncology; Hepatocellular Carcinoma; Hepatoma; TACE; Sintilimab; CVM-1118