Pharmacy and Poisons Board: Applications

List Applications

Protocol No:

ECCT/24/02/10

Date of Protocol:

23-03-2023

Study Title:	A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY EVALUATING ATEZOLIZUMAB AND BEVACIZUMAB, WITH OR WITHOUT TIRAGOLUMAB, IN PATIENTS WITH UNTREATED LOCALLY ADVANCED OR METASTATIC HEPATOCELLULAR CARCINOMA
Study Objectives:	Primary outcome: 1. To evaluate the efficacy of atezolizumab plus bevacizumab plus tiragolumab compared with atezolizumab plus bevacizumab 2.To evaluate the efficacy of atezolizumab plus bevacizumab plus tiragolumab compared with atezolizumab plus bevacizumab Secondary outcome: 1. To evaluate the efficacy of atezolizumab plus bevacizumab plus tiragolumab compared with atezolizumab plus bevacizumab 2. To evaluate the safety of atezolizumab plus bevacizumab plus tiragolumab compared with atezolizumab plus bevacizumab 3. To characterize the PK profile of atezolizumab plus bevacizumab plus tiragolumab 4. To evaluate the immune response to tiragolumab and atezolizumab
Laymans Summary:	The purpose of this study is to assess the efficacy and safety of tiragolumab, an anti-TIGIT monoclonal antibody, when administered in combination with atezolizumab and bevacizumab as first-line treatment, in participants with unresectable, locally advanced or metastatic hepatocellular carcinoma (HCC). Despite recent advances in the first-line treatment setting for patients with HCC, notably cancer immunotherapy (CIT)-based combination regimens, there remains a need for novel therapeutic approaches that target mechanisms of resistance to CIT and provide more durable clinical benefit and improve long-term survival outcomes. TIGIT is believed to play an important role in HCC pathogenesis and resistance to PD-1/PD-L1 blockade. The addition of tiragolumab to atezolizumab plus bevacizumab may augment anticancer immunity, thereby improving clinical outcomes.
Abstract of Study:	Protocol Number: CO44668 Study Name: IMBrave Version Number: 1 Test Compound: Tiragolumab (RO7092284) STUDY RATIONALE The purpose of this study is to assess the efficacy and safety of tiragolumab, an anti-TIGIT monoclonal antibody, when administered in combination with atezolizumab and bevacizumab as first-line treatment, in participants with unresectable, locally advanced or metastatic hepatocellular carcinoma (HCC). Despite recent advances in the first-line treatment setting for patients with HCC, notably cancer immunotherapy (CIT)-based combination regimens, there remains a need for novel therapeutic approaches that target mechanisms of resistance to CIT and provide more durable clinical benefit and improve long-term survival outcomes. TIGIT is believed to play an important role in HCC pathogenesis and resistance to PD-1/PD-L1 blockade. The addition of tiragolumab to atezolizumab plus bevacizumab may augment anticancer immunity, thereby improving clinical outcomes. This study will randomize in a 1:1 ratio to one of two treatment arms: Arm A (experimental arm): Atezolizumab 1200 mg IV Q3W (every 3 weeks) plus bevacizumab 15 mg/kg IV Q3W plus tiragolumab 600 mg IV Q3W Arm B (control arm): Atezolizumab 1200 mg IV Q3W plus bevacizumab 15 mg/kg IV Q3W plus placebo IV Q3W Participants will continue to receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status (e.g., symptomatic deterioration such as pain secondary to disease). Number of patients Approximately 650 patients (1:1 ratio in arm A and B) End of Study: A participant is considered to have completed the study if he or she has completed all phases of the study, including the last visit. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status (e.g., symptomatic deterioration such as pain secondary to disease). The end of this study is defined as the date of the last visit of the last participant in the study (i.e., last participant in the global and extended China enrollment phases combined) or the date at which the last data point required for statistical analysis (i.e., overall survival analysis) or safety follow-up is received from the last participant, whichever occurs later. In addition, the Sponsor may decide to terminate the study at any time. Study Duration The total duration of study participation for each individual is expected to range from 1 day to more than 36 months.