Phase 1/2 Study of Pumitamig Monotherapy or in Combination with Ipilimumab for First-Line Advanced or Unresectable Hepatocellular Carcinoma

The primary objective of this phase 1/2 study is to evaluate the safety and determine the optimal dose response of pumitamig in combination with ipilimumab for the treatment of advanced or unresectable hepatocellular carcinoma. In the phase 2 component, the study aims to assess the efficacy of pumitamig monotherapy and the pumitamig plus ipilimumab combination relative to atezolizumab and bevacizumab.

Secondary objectives include the following:

• Evaluation of safety and tolerability profiles.
• Assessment of pharmacokinetics.
• Identification of potential immunogenicity.
• Determination of therapeutic efficacy.

The study involves a total of 82 patients diagnosed with advanced or unresectable hepatocellular carcinoma. The participant population includes both males and females within the specified age ranges. Inclusion requires individuals to be at least 18 years of age and possess measurable disease via imaging. Eligible participants must demonstrate adequate hepatic function and maintain sufficient performance status to perform daily activities. Furthermore, candidates must not have received prior specific therapeutic interventions for their condition. The study objectives are as follows:

• Determine the safety and optimal dosage of pumitamig in combination with ipilimumab.
• Evaluate the efficacy of pumitamig with ipilimumab, pumitamig monotherapy, or atezolizumab with bevacizumab in reducing tumor size.

This Phase 1/2, open-label, multicenter, randomized study evaluates the safety and efficacy of pumitamig administered either alone or in combination with ipilimumab in participants with first-line advanced or unresectable hepatocellular carcinoma. The phase 1 component focuses on determining safety and identifying the optimal dose, while the phase 2 component compares treatment efficacy regarding objective response rates against a comparator group receiving atezolizumab and bevacizumab. Participants undergo a screening process to confirm eligibility based on age, tumor presence, and liver function. The administration of study drugs is via intravenous infusion. Primary endpoints include the assessment of adverse events and tumor shrinkage, while secondary endpoints involve monitoring progression-free survival, duration of response, pharmacokinetics, and the development of anti-drug antibodies. The trial is estimated to occur between April 2026 and October 2031.

Pumitamig is administered as a concentrate for solution for infusion in two strengths, 20 mg/ml or 50 mg/ml. The route of administration is via intravenous infusion.

Ipilimumab is provided as a concentrate for solution for infusion and is administered through intravenous delivery.

The comparator treatments consist of bevacizumab and atezolizumab, both of which are administered via intravenous infusion.

The efficacy of the investigational treatments in participants with hepatocellular carcinoma will be evaluated using several parameters. The primary efficacy endpoint for the phase 2 component is the objective response rate, defined as the frequency of confirmed complete response or partial response.

Secondary efficacy assessments include:

• Progression-free survival.
• Duration of response.
• Cancer shrinkage.

Pharmacokinetic and immunological parameters will also be assessed, including the measurement of pumitamig levels and ipilimumab levels in the blood. Additionally, the presence of anti-drug antibodies will be monitored.