67O - Outcomes in the Asian subgroup of the phase III HIMALAYA study of tremelimumab (T) plus durvalumab (D) in unresectable hepatocellular carcinoma (uHCC)

Background

In the global, Phase 3 HIMALAYA study (NCT03298451) in uHCC, a single priming dose of T plus regular interval D (STRIDE) significantly improved overall survival (OS) vs sorafenib (S), and D was noninferior to S (Abou-Alfa et al. NEJM Evid 2022; https://doi.org/10.1056/EVIDoa2100070). HCC aetiology varies globally and may influence response to immunotherapy. HBV is predominant in most Asian countries, whereas HCV or nonviral aetiologies are more common in Japan and Western countries. Thus, we analysed outcomes in patients (pts) enrolled in Asia, excluding Japan.

Methods

OS, objective response rate (ORR), duration of response (DoR) and safety for STRIDE, D and S were assessed in pts in Asia (Hong Kong, India, South Korea, Taiwan, Thailand, Vietnam; minus Japan). OS hazard ratios (HRs) and confidence intervals (CIs) were calculated using a Cox proportional hazards model.

Results

The Asia subgroup included 479 pts randomised to STRIDE (n=156), D (n=167) or S (n=156); baseline demographic and disease characteristics were balanced across treatment arms. In Asia vs globally, 62% vs 31% of pts had HBV (HBsAg and/or anti-HBcAb + HBV DNA), 16% vs 27% had HCV (anti-HCV antibodies) and 22% vs 42% had nonviral aetiology. OS was improved for STRIDE vs S in Asia, consistent with the global population (Table). The OS HR for D vs S in Asia was similar to the global population. In Asia and globally, OS at 36 months, ORR and DoR were higher for STRIDE than for D or S. Outcomes in pts of Chinese descent (Hong Kong/Taiwan) were generally consistent with the full Asian subgroup. Grade 3 or 4 treatment-related adverse events were lower for STRIDE and D vs S in Asia (20% and 13% vs 31%) and globally (26% and 13% vs 37%) Table: 67O

*0 pts at risk.

Conclusions

STRIDE improved outcomes vs S for pts in Asia, consistent with the global population. These results support the benefits of STRIDE for pts with uHCC in the Asia-Pacific region, including Hong Kong and Taiwan.

Clinical trial identification

NCT03298451.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Claire Tinderholm, PhD, of CMC Connect, McCann Health Medical Communications, with funding from AstraZeneca, in accordance with Good Publications Practice (GPP3) guidelines.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

S.L. Chan: Financial Interests, Personal, Advisory Board: Eisai, Astra-Zeneca, MSD; Financial Interests, Personal, Invited Speaker: Astra-Zeneca, MSD, Eisai, Roche, IPSEN, BMS, Bayer; Financial Interests, Personal, Research Grant: Eisai, MSD, IPSEN, Bayer, SIRTEX. M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Liiy, Bayer, Takeda, MSD; Financial Interests, Institutional, Research Grant: Otsuka, Sumitomo Dainippon Pharma, EA Pharma, Taiho, Eisai, AbbVie, Gilead Sciences, Takeda, GE Healthcare, Chugai. B. Sangro: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Boston Scientific, Eisai, Ipsen, Roche, Sirtex, Terumo, Incyte, Bayer; Financial Interests, Personal, Invited Speaker: Roche, Sirtex, Eisai, Ipsen, BMS, Incyte, AstraZeneca, Bayer, Astra Zeneca, BMS, Boston Scientific, Roche, Sirtex; Financial Interests, Institutional, Research Grant: BMS, Sirtex; Financial Interests, Institutional, Invited Speaker: Adaptimmune; Non-Financial Interests, Personal, Invited Speaker: International Liver Cancer Association. R.K. Kelley: Financial Interests, Personal, Advisory Board, Compensation for service on advisory board in 2019: Genentech/Roche; Financial Interests, Personal, Other, IDMC membership 2018-2020: Genentech/Roche; Financial Interests, Personal, Advisory Board, 2020: Gilead, Exact Sciences; Financial Interests, Personal, Advisory Board, Advisory board member in 2021: Kinnate; Financial Interests, Institutional, Invited Speaker: Agios, Agios, Astra Zeneca, Astra Zeneca, Bayer, BMS, Eli Lilly, Exelixis, EMD Serono, Genentech/Roche, Merck, Merck, QED, Taiho, Novartis, Relay Therapeutics, Surface Oncology, LOXO Oncology; Financial Interests, Institutional, Research Grant: Partner Therapeutics; Non-Financial Interests, Personal, Advisory Role, IDMC chair and member: Genentech/Roche; Non-Financial Interests, Personal, Principal Investigator: Exelixis, Astra Zeneca. J. Furuse: Financial Interests, Personal, Other, Grant/ research support: Astellas, Chugai Pharma, Daiichi Sankyo, Eisai, Incyte Japan, J-Pharma, Merck Bio, Mochida, MSD, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda, Sanofi, Sumitomo Dainippon Bayer, and Yakult Honsha; Financial Interests, Personal, Other, Consulting fees: Bayer, Chugai Pharma, Daiichi Sankyo, EA Pharma, Eisai, Eli Lilly Japan, Incyte Japan, Kyowa Hakko Kirin, MSD, Mylan EPD, Novartis Pharma, Ono Pharmaceutical, Pfizer, Sanofi, Servier Japan, Taiho Pharmaceutical, Takeda, Teijin Pharma, and Yakult Honsha. P. Sunpaweravong: Financial Interests, Personal, Advisory Board: Roche, Eisai, BMS, AstraZeneca, MSD, Ipsen, Pfizer; Financial Interests, Personal, Invited Speaker: Novartis, BMS, Mundipharma, Bayer. T. Yau: Financial Interests, Personal, Advisory Board, Honorarium: BMS, MSD, AstraZeneCa, Roche. T. Kawaoka: Financial Interests, Institutional, Other, Research funding: AstraZeneca. A. Cheng: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, BAYER Healthcare, AstraZeneca, Genentech/Roche, Merck Sharp Dohme, BeiGene, Ltd., EXELIXIS Ltd., IPSEN Innovation, F. Hoffmanna-La ROCHE Ltd.; Financial Interests, Personal, Invited Speaker: Eisai, Ono Pharmaceutical, Bayer Yakuhin Ltd., Novartis, Amgen Taiwan, Chugai Pharmaceutical; Financial Interests, Personal, Other, Travel: IQVIA. S. Azevedo: Financial Interests, Personal, Other, Grant and research support: Amgen, AstraZeneca, Bristol Myers Squibb, MSD, Novartis, Pfizer, and Roche/Genentech. M.E. Reig Monzon: Financial Interests, Personal, Other, Consultancy: Bayer - Shering Pharma, Ipsen, BMS, Roche, AstraZeneca, Lilly, BTG; Financial Interests, Personal, Other, Paid conferences: Bayer - Shering Pharma, BMS, Roche, Lilly, Gillead, Eisai; Financial Interests, Personal, Research Grant: Bayer - Shering Pharma, Ipsen. E. Assenat: Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: AstraZeneca, Ipsen, Bayer, Roche. M. Yarchoan: Financial Interests, Personal, Advisory Board: Genentech, Eisai, Exelixis, AstraZeneca, Replimune, Hepion; Financial Interests, Institutional, Research Grant, John Hopkins: Genentech, Bristol Myers Squibb, Exelixis, Incyte. A.R. He: Financial Interests, Personal, Other, Advisory Board meeting on management of biliary cancer and HCC: AstraZeneca. M. Makowsky: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. C. Gupta: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Negro: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. G.K. Abou-Alfa: Financial Interests, Personal, Advisory Board: Adicet, Alnylam, Astra Zeneca, Autem, Beigene, Berry Genomics, Boehringer Ingelheim, Celgene, Cend, CytomX, Eisai, Eli Lilly, Exelixis, Flatiron, Genentech/Roche, Genoscience, Helio, Helsinn, Incyte, Ipsen, Merck, Nerviano, Newbridge, Novartis, QED, Redhill, Rafael, Servier, Silenseed, Sobi, Vector, Yiviva; Financial Interests, Personal, Other, IP License: PCT/US2014/031545 filed on March 24, 2014, and priority application Serial No.: 61/804,907; Filed: March 25, 2013; Financial Interests, Institutional, Research Grant: Arcus, AstraZeneca, BioNtech, BMS, Celgene, Flatiron, Genentech/Roche, Genoscience, Incyte, Polaris, Puma, QED, Silenseed, Yiviva; Non-Financial Interests, Personal, Principal Investigator: Astra Zeneca, Yiviva, QED. All other authors have declared no conflicts of interest.