Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma
HIMALAYA
A Randomized, Open-label, Multi-center Phase III Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma
3 other identifiers
interventional
1,324
17 countries
160
Brief Summary
This is a randomized, open-label, multi-center, global, Phase III study to assess the efficacy and safety of durvalumab plus tremelimumab combination therapy and durvalumab monotherapy versus sorafenib in the treatment of patients with no prior systemic therapy for unresectable HCC. The patients cannot be eligible for locoregional therapy
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 hepatocellular-carcinoma
Started Oct 2017
Longer than P75 for phase_3 hepatocellular-carcinoma
160 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 19, 2017
CompletedFirst Posted
Study publicly available on registry
October 2, 2017
CompletedStudy Start
First participant enrolled
October 11, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 27, 2021
CompletedResults Posted
Study results publicly available
June 18, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
August 27, 2026
ExpectedMarch 20, 2026
March 1, 2026
3.9 years
September 19, 2017
August 26, 2022
March 19, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival (OS) - Treme 300 mg x1 Dose + Durva 1500 mg vs Sora 400 mg
OS was defined as the time from the date of randomization until death due to any cause, regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Any participant not known to have died at the DCO date was censored based on the last recorded date on which the participant was known to be alive. If the last known date alive or if the date of death was after the DCO date, participants were censored at the DCO date. This primary outcome measure presents OS analysis of Treme 300mg x1 dose + Durva 1500 mg vs Sora 400 mg at the time of the final analysis DCO (27Aug2021).
From the date of randomization until death due to any cause, assessed up to the data cut-off date (27Aug2021, to a maximum of approximately 46 months).
Secondary Outcomes (16)
Overall Survival (OS) - Durva 1500 mg vs Sora 400 mg
From the date of randomization until death due to any cause, assessed up to the data cut-off date (27Aug2021, to a maximum of approximately 46 months).
Overall Survival (OS) at 18, 24, and 36 Months After Randomization
At 18, 24, and 36 months post-randomization. Assessed at the final analysis DCO (27Aug2021).
Progression Free Survival (PFS)
Tumor scans performed at baseline, every 8 weeks for the first 48 weeks following randomization, and every 12 weeks thereafter until RECIST 1.1-defined progression. Assessed up to DCO (27Aug2021, to a maximum of approximately 46 months)
Time To Progression (TTP)
From the date of randomization until objective tumor progression, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
Objective Response Rate (ORR)
From the date of randomization until objective tumor progression, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
- +11 more secondary outcomes
Study Arms (4)
Arm 1
EXPERIMENTALDurvalumab
Arm 2
EXPERIMENTALDurvalumab in combination with tremelimumab (Regimen 1)
Arm 3
EXPERIMENTALDurvalumab in combination with tremelimumab (Regimen 2)
Arm 4
ACTIVE COMPARATORSorafenib
Interventions
Eligibility Criteria
You may qualify if:
- HCC based on histopathological confirmation
- No prior systemic therapy for HCC
- Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C
- Child-Pugh Score class A
- ECOG performance status of 0 or 1 at enrollment
You may not qualify if:
- Hepatic encephalopathy within past 12 months or requirement for medication to prevent or control encephalopathy
- Clinically meaningful ascites
- Main portal vein tumor thrombosis
- Active or prior documented GI bleeding (eg, esophageal varices or ulcer bleeding) within 12 months
- HBV and HVC co-infection, or HBV and Hep D co-infection
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (160)
Research Site
Los Angeles, California, 90048, United States
Research Site
Orange, California, 92868, United States
Research Site
San Francisco, California, 94158, United States
Research Site
Washington D.C., District of Columbia, 20007, United States
Research Site
Fort Myers, Florida, 33916, United States
Research Site
Jacksonville, Florida, 32224, United States
Research Site
Westwood, Kansas, 66205, United States
Research Site
Baltimore, Maryland, 21231, United States
Research Site
Ann Arbor, Michigan, 48109, United States
Research Site
Rochester, Minnesota, 55905, United States
Research Site
New York, New York, 10065, United States
Research Site
Charlotte, North Carolina, 28262, United States
Research Site
Portland, Oregon, 97213, United States
Research Site
Pittsburgh, Pennsylvania, 15237, United States
Research Site
Dallas, Texas, 74235, United States
Research Site
Dallas, Texas, 75216, United States
Research Site
Dallas, Texas, 75235, United States
Research Site
Houston, Texas, 77030, United States
Research Site
Houston, Texas, 77090, United States
Research Site
Murray, Utah, 84107, United States
Research Site
Barretos, Brazil
Research Site
Curitiba, Brazil
Research Site
Florianópolis, Brazil
Research Site
Porto Alegre, Brazil
Research Site
Rio de Janeiro, Brazil
Research Site
São Paulo, Brazil
Research Site
Calgary, Alberta, T2N 4N2, Canada
Research Site
Edmonton, Alberta, T6G 1Z2, Canada
Research Site
Hamilton, Ontario, L8V 5C2, Canada
Research Site
Kingston, Ontario, K7L 2V7, Canada
Research Site
London, Ontario, N6A 4L6, Canada
Research Site
Toronto, Ontario, M4N 3M5, Canada
Research Site
Montreal, Quebec, H2X 0A9, Canada
Research Site
Québec, Quebec, G1R 2J6, Canada
Research Site
Sherbrooke, Quebec, J1H 5N4, Canada
Research Site
Beijing, China
Research Site
Changchun, China
Research Site
Changsha, China
Research Site
Chengdu, China
Research Site
Dalian, China
Research Site
Fuzhou, China
Research Site
Guangzhou, China
Research Site
Hangzhou, China
Research Site
Harbin, China
Research Site
Hefei, China
Research Site
Nanchang, China
Research Site
Nanjing, China
Research Site
Nanning, China
Research Site
Shanghai, China
Research Site
Suzhou, China
Research Site
Wuhan, China
Research Site
Xi'an, China
Research Site
Zhengzhou, China
Research Site
Clichy, France
Research Site
Lille, France
Research Site
Marseille, France
Research Site
Montpellier, France
Research Site
Nancy, France
Research Site
Nantes, France
Research Site
Nice, France
Research Site
Pessac, France
Research Site
Poitiers, France
Research Site
Reims, France
Research Site
Rouen, France
Research Site
Saint-Etienne, France
Research Site
Toulouse, France
Research Site
Villejuif, France
Research Site
Aachen, Germany
Research Site
Cologne, Germany
Research Site
Essen, Germany
Research Site
Hanover, Germany
Research Site
Heidelberg, Germany
Research Site
Leipzig, Germany
Research Site
Mainz, Germany
Research Site
München, Germany
Research Site
Tübingen, Germany
Research Site
Ulm, Germany
Research Site
Hong Kong, Hong Kong
Research Site
Bangalore, India
Research Site
Bhubneshwar, India
Research Site
Chennai, India
Research Site
Hubli, India
Research Site
Hyderabad, India
Research Site
Karmsad, India
Research Site
Mumbai, India
Research Site
Nashik, India
Research Site
New Delhi, India
Research Site
Benevento, Italy
Research Site
Meldola, Italy
Research Site
Milan, Italy
Research Site
Naples, Italy
Research Site
Perugia, Italy
Research Site
Pisa, Italy
Research Site
Roma, Italy
Research Site
Rozzano, Italy
Research Site
Bunkyoku, Japan
Research Site
Chiba, Japan
Research Site
Fukuoka, Japan
Research Site
Hiroshima, Japan
Research Site
Iizuka, Japan
Research Site
Kanazawa, Japan
Research Site
Kōtoku, Japan
Research Site
Kumamoto, Japan
Research Site
Kurume, Japan
Research Site
Matsuyama, Japan
Research Site
Mitakashi, Japan
Research Site
Musashino, Japan
Research Site
Nagoya, Japan
Research Site
Okayama, Japan
Research Site
Osaka, Japan
Research Site
Ōgaki, Japan
Research Site
Ōsaka-sayama, Japan
Research Site
Saga, Japan
Research Site
Sapporo, Japan
Research Site
Shiwa, Japan
Research Site
Suntogun, Japan
Research Site
Tsu, Japan
Research Site
Yokohama, Japan
Research Site
Moscow, Russia
Research Site
Murmansk, Russia
Research Site
Nizhny Novgorod, Russia
Research Site
Novosibirsk, Russia
Research Site
Obninsk, Russia
Research Site
Omsk, Russia
Research Site
Saint Petersburg, Russia
Research Site
Ufa, Russia
Research Site
Ilsan, Gyeonggi-do, 10408, South Korea
Research Site
Seongnam-si, Gyeonggi-do, 13620, South Korea
Research Site
Busan, 49241, South Korea
Research Site
Daegu, 41944, South Korea
Research Site
Seoul, 3080, South Korea
Research Site
Seoul, 3722, South Korea
Research Site
Seoul, 5505, South Korea
Research Site
Seoul, 6351, South Korea
Research Site
Barcelona, Spain
Research Site
Madrid, Spain
Research Site
Oviedo, Spain
Research Site
Pamplona Madrid, Spain
Research Site
Santander, Spain
Research Site
Chiayi City, Taiwan
Research Site
Kaohsiung City, Taiwan
Research Site
Taichung, Taiwan
Research Site
Tainan, Taiwan
Research Site
Taipei, Taiwan
Research Site
Taoyuan District, Taiwan
Research Site
Bangkok, Thailand
Research Site
Chang Mai, Thailand
Research Site
Khon Kaen, Thailand
Research Site
Phitsanulok, Thailand
Research Site
Songkhla, Thailand
Research Site
Dnipro, Ukraine
Research Site
IvanoFrankivsk, Ukraine
Research Site
Kharkiv, Ukraine
Research Site
Kropyvnitskyi, Ukraine
Research Site
Kyiv, Ukraine
Research Site
Lviv, Ukraine
Research Site
Odesa, Ukraine
Research Site
Uzhhorod, Ukraine
Research Site
Hanoi, Vietnam
Research Site
Hochiminh, Vietnam
Related Publications (7)
Chan SL, Kudo M, Sangro B, Kelley RK, Kim JH, Pham B, Hong JY, Waldschmidt DT, Marino D, Joycelyn Lee JX, Gerolami R, Burgoyne AM, Li Q, Nakamura H, Sun P, Baur B, Rimassa L. Early Safety Results from the Phase 3b SIERRA Study of Durvalumab and Tremelimumab as First-Line Treatment for Participants with Unresectable Hepatocellular Carcinoma and a Poor Prognosis. Liver Cancer. 2025 Dec 18. doi: 10.1159/000549955. Online ahead of print.
PMID: 41585428DERIVEDRimassa L, Chan SL, Sangro B, Lau G, Kudo M, Reig M, Breder V, Ryu MH, Ostapenko Y, Sukeepaisarnjaroen W, Varela M, Tougeron D, Crysler OV, Bouattour M, Van Dao T, Tam VC, Faccio A, Furuse J, Jeng LB, Kang YK, Kelley RK, Paskow MJ, Ran D, Xynos I, Kurland JF, Negro A, Abou-Alfa GK. Five-year overall survival update from the HIMALAYA study of tremelimumab plus durvalumab in unresectable HCC. J Hepatol. 2025 Oct;83(4):899-908. doi: 10.1016/j.jhep.2025.03.033. Epub 2025 Apr 11.
PMID: 40222621DERIVEDLau G, Abou-Alfa GK, Cheng AL, Sukeepaisarnjaroen W, Van Dao T, Kang YK, Thungappa SC, Kudo M, Sangro B, Kelley RK, Furuse J, Park JW, Sunpaweravong P, Fasolo A, Yau T, Kawaoka T, Azevedo S, Reig M, Assenat E, Yarchoan M, He AR, Makowsky M, Gupta C, Negro A, Chan SL. Outcomes in the Asian subgroup of the phase III randomised HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. J Hepatol. 2025 Feb;82(2):258-267. doi: 10.1016/j.jhep.2024.07.017. Epub 2024 Jul 31.
PMID: 39089633DERIVEDSangro B, Galle PR, Kelley RK, Charoentum C, De Toni EN, Ostapenko Y, Heo J, Cheng AL, Wilson Woods A, Gupta C, Abraham J, McCoy CL, Patel N, Negro A, Vogel A, Abou-Alfa GK. Patient-Reported Outcomes From the Phase III HIMALAYA Study of Tremelimumab Plus Durvalumab in Unresectable Hepatocellular Carcinoma. J Clin Oncol. 2024 Aug 10;42(23):2790-2799. doi: 10.1200/JCO.23.01462. Epub 2024 May 28.
PMID: 38805668DERIVEDAbou-Alfa GK, Lau G, Kudo M, Chan SL, Kelley RK, Furuse J, Sukeepaisarnjaroen W, Kang YK, Van Dao T, De Toni EN, Rimassa L, Breder V, Vasilyev A, Heurgue A, Tam VC, Mody K, Thungappa SC, Ostapenko Y, Yau T, Azevedo S, Varela M, Cheng AL, Qin S, Galle PR, Ali S, Marcovitz M, Makowsky M, He P, Kurland JF, Negro A, Sangro B. Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma. NEJM Evid. 2022 Aug;1(8):EVIDoa2100070. doi: 10.1056/EVIDoa2100070. Epub 2022 Jun 6.
PMID: 38319892DERIVEDAddendum 1: Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of hepatocellular carcinoma. J Immunother Cancer. 2023 Sep;11(9):e002794add1. doi: 10.1136/jitc-2021-002794add1. No abstract available.
PMID: 37678916DERIVEDPatel TH, Brewer JR, Fan J, Cheng J, Shen YL, Xiang Y, Zhao H, Lemery SJ, Pazdur R, Kluetz PG, Fashoyin-Aje LA. FDA Approval Summary: Tremelimumab in Combination with Durvalumab for the Treatment of Patients with Unresectable Hepatocellular Carcinoma. Clin Cancer Res. 2024 Jan 17;30(2):269-273. doi: 10.1158/1078-0432.CCR-23-2124.
PMID: 37676259DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca Clinical Study Information Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 19, 2017
First Posted
October 2, 2017
Study Start
October 11, 2017
Primary Completion
August 27, 2021
Study Completion (Estimated)
August 27, 2026
Last Updated
March 20, 2026
Results First Posted
June 18, 2023
Record last verified: 2026-03