A Study of TPST-1120 With Atezolizumab Plus Bevacizumab in Patients With Unresectable or Metastatic HCC Not Previously Treated With Systemic Therapy

This is a Phase 3, randomized, multicenter, double-blind, Pbo-controlled study of TPST-AB versus Pbo-AB in patients with unresectable or metastatic HCC not previously treated with systemic therapy.

The study will consist of a screening period, a treatment period, and a follow-up period.

The purpose of this study is to measure the safety and efficacy of TPST-1120 in combination with atezolizumab plus bevacizumab compared with placebo plus atezolizumab plus bevacizumab in patients with unresectable or metastatic HCC who have received no prior systemic treatment. Study details include:

* Study duration: until death, loss to follow-up, withdrawal of consent, or study termination, whichever occurs first\] * Treatment duration: until unacceptable toxicity or loss of clinical benefit * Visit frequency: every 21 days

Approximately 740 patients are planned to be randomized and enrolled.

Eligible patients will be randomized in a 1:1 ratio to receive study intervention with the combination of TPST-AB or Pbo-AB as follows:

* Active arm: TPST-1120 600 mg per os (PO) twice daily (BID) with atezolizumab 1200 mg intravenously (IV) every 3 weeks (Q3W) and bevacizumab 15 mg/kg IV Q3W * Control arm: Placebo PO BID with atezolizumab 1200 mg IV Q3W and bevacizumab 15 mg/kg IV Q3W

Patients may continue to receive study intervention until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status (e.g., symptomatic deterioration such as pain secondary to disease). In the absence of unacceptable toxicity, patients who meet criteria for disease progression per RECIST v1.1 while receiving study intervention will be permitted to continue the study intervention if they meet all of the following criteria:

* Evidence of clinical benefit, as determined by the investigator following a review of all available data * Absence of symptoms and signs (including laboratory values, such as new or worsening hypercalcemia) indicating unequivocal progression of disease * Absence of decline in Eastern Cooperative Oncology Group (ECOG) performance status that can be attributed to disease progression * Absence of tumor progression at critical anatomical sites (e.g., leptomeningeal disease) that would require urgent alternative medical intervention