205TiP - IMPACT: Randomized, multicenter, phase III study evaluating the efficacy of immunotherapy (atezolizumab) plus anti-VEGF therapy (bevacizumab) in combination with transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma (HCC)

Background

The combination of atezolizumab (Atezo) and bevacizumab (Bev) is recommended as a first-line treatment for unresectable HCC (uHCC) in the Japanese guidelines for liver cancer treatment, as well as in the guidelines of the Barcelona Clinic Liver Cancer (BCLC) Group and the American Association for the Study of Liver Diseases, based on the results of the IMbrave150 trial. In the subgroup analysis of the IMbrave150 trial, patients with stable disease (SD), accounting for approximately 40% of the total population, had statistically significantly shorter overall survival (OS) compared to patients with complete response (CR) or partial response (PR) (SD: median 17.1 months, CR+PR: median not reached, P<0.0001). Prolonging the prognosis of the SD group is one of the unmet medical needs for uHCC. On the other hand, transcatheter arterial chemoembolization (TACE) could achieve a high local effect and control intrahepatic lesions. In addition, TACE has been reported to activate anti-tumor immunity and therefore, might synergistically enhance the efficacy of Atezo plus Bev.

Trial design

This is a multicenter, phase III study of patients with uHCC who have BCLC-B stage (including a single tumor with a diameter ≥5 cm) or BCLC-C stage (excluding Vp3 or 4) and Child-Pugh A liver function. Cohorts will be divided based on imaging evaluation at 12 weeks after Atezo plus Bev treatment. Patients with SD (RECIST ver.1.1) will be randomized (randomized cohort) to receive Atezo plus Bev with or without TACE (1:1 allocation) to investigate its contribution to extending OS (primary endpoint). In addition, patients with CR or PR based on imaging evaluation at 12 weeks after Atezo plus Bev treatment (ABC-conversion cohort) will be prospectively followed to evaluate the conversion rate (primary endpoint) and the prognosis of patients who receive conversion therapy.

Clinical trial identification

jRCT:s051230037.

Legal entity responsible for the study

The authors.

Funding

Chugai Pharmaceutical Co., Ltd.

Disclosure

T. Yamashita: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Lilly, Bayer, Takeda; Financial Interests, Institutional, Local PI: Bristol-Myers, MSD, Ono, Abbie, Eisai; Financial Interests, Institutional, Other, Sub-PI: Chugai. Y. Inaba: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai; Financial Interests, Institutional, Local PI: Eisai, AstraZeneca, Chugai. M. Ikeda: Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Eli Lilly Japan, Eisai, NIHON Servier, Novartis, MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Chugai, Eli Lilly Japan, Eisai, NIHON Servier, Novartis, Taiho, Yakult, Teijin Pharma, AbbVie, Abbott Japan, Fujifilm Toyama Chemical, Incyte Biosciences Japan, Takeda, Ono, MSD, Taisho Pharmaceutical, Nippon Kayaku, Guardant Health Japan; Financial Interests, Institutional, Coordinating PI: Bayer, Bristol Myers Squibb, Eisai, AstraZeneca, Eli Lilly Japan, Chugai Pharmaceutical, MSD, Ono, Novartis, J-Pharma, Pfizer, Chiome Bioscience, NIHON Servier, Delta-Fly Pharma, Syneos Health, Merus.N.V., Merck biopharma, Boehringer Ingelheim, Invitae; Financial Interests, Personal, Steering Committee Member: Chugai, NIHON Servier, Takeda, Novartis, Eisai, Rakuten Medical. M. Sone: Financial Interests, Personal, Invited Speaker: Covidien Japan, Cardinal Health, AstraZeneca, CANON Medical Systems, Guerbet; Financial Interests, Personal, Advisory Board: Boston Scientific; Financial Interests, Institutional, Research Grant: CANON Medical Systems, Dream Medical Partners; Non-Financial Interests, Personal, Member: ASCO. K. Tsuchiya: Financial Interests, Personal, Invited Speaker: Chugai, Eisai, Takeda, AstraZeneca; Financial Interests, Personal, Advisory Board: Chugai. T. Tada: Financial Interests, Personal, Invited Speaker: Eisai, AbbVie, Chugai. T. Kodama: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co, AstraZeneca, Eisai Co.Ltd, Takeda pharmaceutical Co, AbbVie, Gilead Sciences. T. Kuzuya: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co. S. Ogasawara: Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Eisai; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Funding: Chugai; Financial Interests, Personal, Research Grant: Eisai. M. Ueno: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Incyte, MSD, Nihon Servier, Ono Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical; Financial Interests, Personal, Advisory Board: Nippon Boehringer Ingelheim, Novartis; Financial Interests, Institutional, Local PI: Astellas Pharma, AstraZeneca, Chugai Pharmaceutical, DFP, Daiichi Sankyo, Eisai, Incyte, MSD, Merck Biopharma, Ono Pharmaceutical, Taiho Pharmaceutical, Novartis. M. Moriguchi: Financial Interests, Personal, Invited Speaker: Eisai Co., Ltd., Bayer Yakuhin, Ltd., Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Takeda Pharmaceutical Company Limited; Financial Interests, Personal, Advisory Board: Eisai Co., Ltd., Bayer Yakuhin, Ltd., Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., AztraZeneca K.K.; Financial Interests, Institutional, Funding: MSD K.K. Eisai Co., Ltd., Bristol Myers Squibb K.K., Bayer Yakuhin, Ltd., Eisai Co., Ltd. K. Ueshima: Financial Interests, Personal, Invited Speaker, Concurrent roles with an advisory board: Chugai, Eisai, Takeda, Lilly Japan; Financial Interests, Personal, Invited Speaker: AstraZeneca, Otsuka, Taiho, Sumitomo, MSD, Kowa, EA pharma, AbbVie, Aska; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Local PI: Chugai. T. Takehara: Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Institutional, Research Grant: Chugai. T. Hamano: Financial Interests, Personal, Invited Speaker: Chugai pharmaceutical co. ltd.; Financial Interests, Institutional, Officer: P4 statistics co. ltd.; Financial Interests, Personal, Stocks/Shares: P4 statistics co. ltd. M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Liiy, Bayer, Takeda, AstraZeneca; Financial Interests, Institutional, Research Grant: Otsuka, EA Pharma, Taiho, Eisai, AbbVie, GE Healthcare, Chugai. All other authors have declared no conflicts of interest.