Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Proffered Paper session 1: GI, upper digestive

LBA36 - Final analysis of RATIONALE-301: Randomized, phase III study of tislelizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma


10 Sep 2022


Proffered Paper session 1: GI, upper digestive


Tumour Site

Gastrointestinal Cancers


Masatoshi Kudo


Annals of Oncology (2022) 33 (suppl_7): S808-S869. 10.1016/annonc/annonc1089


S. Qin1, M. Kudo2, T. Meyer3, R.S. Finn4, A. Vogel5, Y. Bai6, Y. Guo7, Z. Meng8, T. Zhang9, T. Satoh10, A. Hiraoka11, D. Marino12, E. Assenat13, L.S. Wyrwicz14, M. Calvo Campos15, K. Hsing-Tao16, F. Boisserie17, S. Li18, Y. Chen19, A.X. Zhu20

Author affiliations

  • 1 Cancer Center Of Jinling Hospital, Nanjing University of Chinese Medicine, 210002 - Nanjing/CN
  • 2 Department Of Gastroenterology And Hepatology, Kindai University Faculty of Medicine, 589-8511 - Osaka/JP
  • 3 Department Of Oncology, Royal Free Hospital NHS Trust and UCL Cancer Institute, WC1 E6JD - London/GB
  • 4 Department Of Medicine, Division Of Hematology/oncology, University of California Los Angeles, 90095 - Los Angeles/US
  • 5 Department Of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 - Hannover/DE
  • 6 Department Of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, 150081 - Harbin/CN
  • 7 Center For Infectious Diseases And Liver Diseases, Nanfang Hospital, Southern Medical University, Guangzhou/CN
  • 8 Department Of Integrative Oncology, Fudan University Shanghai Cancer Hospital, Shanghai/CN
  • 9 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022 - Wuhan/CN
  • 10 Department Of Frontier Science For Cancer And Chemotherapy, Osaka University, Osaka/JP
  • 11 Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama/JP
  • 12 Division Of Medical Oncology, Ordine Mauriziano Hospital, 10128 - Turin/IT
  • 13 Department Of Medical Oncology, Montpellier University Hospital, 34298 - Montpellier/FR
  • 14 Department Of Oncology And Radiotherapy, Maria Sklodowska-Curie National Cancer Research Institute, Warsaw/PL
  • 15 Department Of Medical Oncology, Institut Català d'Oncologia, Barcelona/ES
  • 16 Department Of Gastroenterology, Chi Mei Medical Center, Tainan/TW
  • 17 Clinical Development – Solid Tumor, BeiGene, Ltd., Ridgefield Park/US
  • 18 Statistics And Data Science, BeiGene, Ltd., Ridgefield Park/US
  • 19 Clinical Development – Solid Tumor, BeiGene (Beijing) Co., Ltd., Beijing/CN
  • 20 Department Of Medicine, Massachusetts General Hospital Cancer Center, Boston, MA, United States; Jiahui International Cancer Center, Jiahui Health, Shanghai/CN


Login to access the resources on OncologyPRO.

Abstract LBA36


Tislelizumab (TIS), an anti-PD-1 monoclonal antibody, has demonstrated durable responses and was well tolerated as monotherapy in 2L+ treatment in patients (pts) previously treated systemically for unresectable HCC (Ducreux et al, 2021). TIS has been further evaluated against sorafenib (SOR) in a global randomized Phase 3 study (RATIONALE-301; NCT03412773) as 1L treatment in adult pts with unresectable HCC.


Systemic therapy-naïve adults with histologically confirmed HCC BCLC Stage B/C who were not amenable to or progressed after loco-regional therapy, Child-Pugh A, with ≥1 measurable lesion per RECIST v1.1, and an ECOG PS ≤1 were eligible. Pts were randomized 1:1 to receive TIS (200 mg IV Q3W) or SOR (400 mg PO BID) until disease progression, intolerable toxicity, withdrawal, or no longer benefiting from therapy. The primary endpoint was OS; secondary endpoints included ORR, PFS, and DOR by blinded independent review committee, and safety. Non-inferiority of OS between TIS and SOR was tested against the non-inferiority margin of 1.08.


A total of 674 pts were randomized (n=342, TIS; n=332, SOR); at data cutoff (11 Jul 2022) minimum study follow up was 33 months (mo). In this final analysis, RATIONALE-301 met its primary endpoint of OS non-inferiority (mOS: 15.9 mo [TIS] vs 14.1 mo [SOR]; stratified HR: 0.85 [95.003% CI: 0.712, 1.019]). TIS was associated with higher ORR (14.3% vs 5.4%) and more durable responses (mDoR: 36.1 mo vs 11.0 mo) compared with SOR. Median PFS with TIS was 2.2 mo and 3.6 mo with SOR (HR: 1.1 [95% CI: 0.92, 1.33]). Median treatment duration was longer with TIS vs SOR (4.1 mo vs 2.7 mo). The safety profiles for both treatments were consistent with prior reports. Incidence rates of grade ≥3 AEs (48.2% vs 65.4%) and AEs leading to discontinuation (10.9% vs 18.5%) were lower with TIS compared with SOR; AEs leading to death were low across both treatments (4.4%, TIS; 5.2%, SOR). Immune-mediated AEs occurring in ≥5% TIS-treated pts were hepatitis (5.3%) and hypothyroidism (5.3%).


Single-agent TIS demonstrated clinically meaningful OS benefit that was non-inferior to SOR with a favorable safety profile as a 1L treatment option for pts with unresectable HCC.

Clinical trial identification


Editorial acknowledgement

This study was sponsored by BeiGene, Ltd. Medical writing support, under the direction of the authors, was provided by Arezou Seyed Hossein, MPharm, of Ashfield MedComms, an Ashfield Health company, and was funded by BeiGene, Ltd.

Legal entity responsible for the study

BeiGene, Ltd.


BeiGene, Ltd.


M. Kudo: Financial Interests, Invited Speaker: Eli Lilly, Bayer, Eisai, Chugai, Takeda; Financial Interests, Research Grant: Gilead Sciences, Taiho, Sumitomo Dainippon Pharma, Takeda, Otsuka, EA Pharma, AbbVie, Eisai. T. Meyer: Financial Interests, Advisory Board: MSD, Ipsen, AstraZeneca, Eisai, Roche, Adaptimmune; Financial Interests, Institutional, Funding, Grant to institution: MSD, BTG. R.S. Finn: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, CStone, Bayer, BMS, Exelixis, Eli Lilly, Eisai,Hengrui, Merck, Pfizer, Roche/ Genenentech; Financial Interests, Institutional, Research Grant: Adaptimmune, Bayer, BMS, Eli Lilly, Eisai,Merck, Pfizer, Roche/ Genentech; Non-Financial Interests, Principal Investigator: Eisai, Merck, Roche/Genentech, BMS, Pfizer. A. Vogel: Financial Interests, Invited Speaker: Roche, Bayer, BMS, Lilly, EISAI, AstraZeneca, Ipsen, MSD, Sirtex, BTG, Servier, Terumo, Imaging Equipment Ltd (AAA); Financial Interests, Advisory Board: Roche, Bayer, BMS, Lilly, EISAI, AstraZeneca, Ipsen, MSD, Sirtex, BTG, Servier, Terumo, Imaging Equipment Ltd (AAA). A. Hiraoka: Non-Financial Interests, Speaker’s Bureau: Chugai Pharma., Lilly, Beyer. D. Marino: Financial Interests, Advisory Board: Roche, MSD; Financial Interests, Sponsor/Funding, Travel and meeting expenses: Pierre-Fabre. E. Assenat: Financial Interests, Advisory Board: Roche, Astra Zeneca, Servier,Ipsen. M. Calvo Campos: Financial Interests, Advisory Role: Roche/Eisai/Bayer/MSD. K. Hsing-Tao: Financial Interests, Principal Investigator: BeiGene Ltd. F. Boisserie: Financial Interests, Full or part-time Employment: BeiGene; Financial Interests, Stocks/Shares: BeiGene. S. Li: Financial Interests, Full or part-time Employment: BeiGene, Ltd. Y. Chen: Financial Interests, Full or part-time Employment: BeiGene, Ltd. A.X. Zhu: Financial Interests, Advisory Role, Consulting fee: Merck, Roche, Sanofi, Eisai, Exelixis, Bayer, Lilly. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.