147P - Four-year overall survival (OS) update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma (uHCC)

Background

In the primary analysis (data cut-off [DCO]: 27 August 2021) of the phase 3 HIMALAYA study (NCT03298451) in uHCC, STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved OS vs sorafenib; durvalumab was noninferior to sorafenib (Abou-Alfa et al. NEJM Evid 2022). Here, we report an updated 4-year OS analysis of HIMALAYA.

Methods

Participants with uHCC and no previous systemic treatment were randomised to STRIDE (tremelimumab 300 mg for one dose plus durvalumab 1500 mg every 4 weeks [Q4W]), durvalumab (1500 mg Q4W) or sorafenib (400 mg twice daily). DCO was 23 January 2023 (STRIDE OS data maturity, 78%). OS and serious treatment-related adverse events (TRAEs) were assessed. In addition, baseline demographics and disease characteristics were assessed in long-term survivors (LTS; surviving ≥36 months beyond randomisation).

Results

Follow-up duration was approximately 4 years across arms (Table). The OS HR vs sorafenib and estimated 36-month OS rate for STRIDE were consistent with the primary analysis. The 48-month OS rate remained higher for STRIDE (25.2%) vs sorafenib (15.1%). No new serious TRAEs occurred after the primary analysis for STRIDE. Durvalumab OS noninferiority to sorafenib and safety was consistent with the primary analysis. Baseline demographics, clinical characteristics, subsequent therapies and tremelimumab rechallenge for LTS in the STRIDE arm were generally consistent with the full analysis set, suggesting that LTS were not from any particular subgroup.

Conclusions

These data reinforce the sustained, long-term OS benefit of STRIDE vs sorafenib in a diverse uHCC population, demonstrating unprecedented 3- and 4-year OS rates and longest follow-up to date in phase 3 uHCC studies. STRIDE maintained a tolerable safety profile, with no new serious safety events. This abstract was originally presented at the 2023 World Congress on Gastrointestinal Cancer. Table: 147P

Updated analysis of HIMALAYA with 4 years of follow-up (DCO: 23 January 2023)

∗OS HRs and CIs were calculated using a Cox proportional hazards model.

Clinical trial identification

NCT0329845.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Claire Tinderholm, PhD, of CMC Connect, a division of IPG Health Medical Communications, funded by AstraZeneca, in accordance with Good Publication Practice (GPP 2022) guidelines.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

S.L. Chan: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, MSD, BMS, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Eisai, Roche, Ipsen, BMS; Financial Interests, Personal, Research Grant: Eisai, MSD. B. Sangro: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Boston Scientific, Roche, Sirtex, Terumo, Bayer, Adaptimmune; Financial Interests, Personal, Invited Speaker: Roche, Sirtex, Eisai, Ipsen, Incyte, AstraZeneca, Astellas Pharma; Financial Interests, Institutional, Research Grant: BMS, Sirtex; Financial Interests, Personal, Coordinating PI: AstraZeneca; Financial Interests, Personal, Steering Committee Member: BMS, Boston Scientific, Roche. R.K. Kelley: Financial Interests, Institutional, Speaker, Consultant, Advisor: Agios, AstraZeneca, Exelixis, Ipsen, and MSD; Financial Interests, Personal, Speaker, Consultant, Advisor: Exact Sciences, Ipsen, Kinnate, Regeneron, and Tyra Biosciences; Financial Interests, Institutional, Research Funding: Adaptimmune, Agios, AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, EMD Serono, Exelixis, Genentech, Loxo Oncology, MSD, Novartis, Partner Therapeutics, QED, Relay Therapeutics, Roche, Surface Oncology, and Taiho. G. Lau: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca. 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. E.N. De Toni: Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb and Falk; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Eli Lilly, Ipsen, Mallinckrodt, MSD, Pfizer, Terumo, and Roche; Financial Interests, Personal, Research Funding: Arqule, AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, Ipsen, and Roche; Financial Interests, Personal, Other, Travel expenses: Arqule, AstraZeneca, Bayer, Bristol Myers Squibb, Celsion, and Roche. J. Furuse: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Bayer, Eisai, Eli Lilly Japan, MSD, Yakult Honsha, Chugai Pharma, Novartis Pharma, AstraZeneca, Pfizer, Takeda, Taiho Pharmaceutical, Sannofy, Mylan EPD, EA Pharma, Kyowa Hakko Kirin, Daiichi Sankyo, Teijin pharma, Servier Japan, Incy; Financial Interests, Personal, Advisory Board: Fuji film, Mudi Pharma, Onco Therapy Science, Merck Bio, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Chugai Pharma, Astellas, AstraZeneca, Takara bio, Delta-Fly-Pharma, Incyte Japan; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical, MSD, Merck Bio, J-Pharma, Taiho Pharmaceutical, Takeda, Chugai Pharma, AstraZeneca, Yakult Honsha, Eisai, Daiichi Sankyo, Mochida, Sanofy, Sumitomo Dainippon Bayer, Astellas, Incyte Japan; Financial Interests, Personal, Steering Committee Member: Merck Bio, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Astellas, AstraZeneca, Incyte Japan. Y. Kang: Financial Interests, Personal, Advisory Board: ALX Oncology, Zymeworks, Amgen, Novartis, Macrogenics, Daehwa, Blueprint, Surface Oncology, BMS, Merck, Roche, Liscure. P.R. Galle: Financial Interests, Personal, Other, Grant/research funding, and/or honoraria: Adaptimmune, AstraZeneca, Bayer, Bristol Myers Squibb, Boston Scientific, Eisai, Eli Lilly, F. Hoffmann-La Roche, Guerbet, Ipsen, MSD, and Sirtex Medical. L. Rimassa: Financial Interests, Personal, Advisory Board, Consulting and advisory role: AstraZeneca, Basilea, Bayer, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Jazz Pharmaceuticals, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, Zymeworks; Financial Interests, Personal, Invited Speaker, Lecture fees: AstraZeneca, Bayer, BMS, Incyte, Ipsen, Roche, Servier; Financial Interests, Personal, Other, Travel expenses: AstraZeneca; Financial Interests, Institutional, Steering Committee Member: Exelixis, Incyte, Ipsen, Nerviano Medical Sciences, Roche; Financial Interests, Institutional, Coordinating PI, National (Italian) coordinating PI: AstraZeneca, BeiGene, Zymeworks; Financial Interests, Institutional, Local PI: Agios, Eisai, Fibrogen, Lilly, MSD; Financial Interests, Institutional, Funding: Ipsen; Financial Interests, Institutional, Coordinating PI, European PI: AstraZeneca. A. Heurgue: Financial Interests, Personal, Speaker, Consultant, Advisor: AbbVie, AstraZeneca, Bayer, Intercept, and Ipsen. V.C. Tam: Financial Interests, Institutional, Advisory Board, Grant/research funding: Eisai, Ipsen, and Roche; consulting fees from Incyte, Ipsen, and Roche; Financial Interests, Personal, Other, Honoraria: Apobiologix, AstraZeneca, Eisai, Incyte, Ipsen, and Roche. T.V. Dao: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Bayer, Eisai, Ipsen, MSD, Novartis, Pfizer, Pierre Faber, Roche, and Taiho Pharmaceutical. S. Chiradoni Thungappa: Financial Interests, Institutional, Advisory Board, Grant/ research funding: AstraZeneca and Eisai; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca. V. Breder: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Eisai, F. Hoffman-La Roche, and Merck; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Eisai, F. Hoffman-La Roche, and Merck; Financial Interests, Personal, Other, Travel grants: Bayer Healthcare and F. Hoffman-La Roche. Y.V. Ostapenko: Financial Interests, Institutional, Other, Principal Investigator: Jounce Therapeutics. M.E. Reig Monzon: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Ipsen, Lilly, Roche, and Universal DX; Financial Interests, Personal, Invited Speaker: Bayer, Bristol Myers Squibb, BTG, Eisai, Gilead Sciences, Lilly, and Roche; Financial Interests, Personal, Other, Grant/ research funding: Bayer and Ipsen. C. Gupta: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. G.K. Abou-Alfa: Financial Interests, Personal, Other, Grant/ research funding: Arcus, AstraZeneca, BioNtech, Bristol Myers Squibb, Celgene, Flatiron, Genentech/Roche, Genoscience, Incyte, Polaris, Puma, QED, Silenseed, and Yiviva; Financial Interests, Personal, Speaker, Consultant, Advisor: Adicet, Alnylam, AstraZeneca, 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, Redhil. All other authors have declared no conflicts of interest.