Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma

NCT ID: NCT03298451

Last Updated: 2026-01-14

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1324 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-11

Study Completion Date

2026-08-27

Brief Summary

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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

Detailed Description

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The study population includes patients 18 years of age or older with advanced HCC, Barcelona Clinic Liver Cancer stage B not eligible for locoregional therapy or stage C, and Child-Pugh A classification liver disease. Patients must not have received any prior systemic therapy for unresectable HCC.

Patients in all treatment arms may continue receiving their originally assigned treatment, at the Investigator's discretion, until progression

Patients in all arms with confirmed PD who, in the Investigator's opinion, continue to receive benefit from their assigned treatment and meet the criteria for treatment in the setting of PD may continue to receive their assigned treatment.

If a patient discontinues study drug(s) due to disease progression, the patient will enter survival follow-up. Patients who have discontinued treatment due to toxicity or symptomatic deterioration or who have commenced subsequent anticancer therapy, will have tumor assessments until confirmed PD and will be followed for survival

Conditions

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Hepatocellular Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1

Durvalumab

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

Durvalumab IV (intravenous infusion).

Arm 2

Durvalumab in combination with tremelimumab (Regimen 1)

Group Type EXPERIMENTAL

Tremelimumab (Regimen 1)

Intervention Type DRUG

Tremelimumab IV (intravenous infusion).

Durvalumab (Regimen 1)

Intervention Type DRUG

Durvalumab IV (intravenous infusion).

Arm 3

Durvalumab in combination with tremelimumab (Regimen 2)

Group Type EXPERIMENTAL

Tremelimumab (Regimen 2)

Intervention Type DRUG

Tremelimumab IV (intravenous infusion).

Durvalumab (Regimen 2)

Intervention Type DRUG

Durvalumab IV (intravenous infusion).

Arm 4

Sorafenib

Group Type ACTIVE_COMPARATOR

Sorafenib

Intervention Type DRUG

Sorafenib, as per standard of care

Interventions

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Durvalumab

Durvalumab IV (intravenous infusion).

Intervention Type DRUG

Tremelimumab (Regimen 1)

Tremelimumab IV (intravenous infusion).

Intervention Type DRUG

Tremelimumab (Regimen 2)

Tremelimumab IV (intravenous infusion).

Intervention Type DRUG

Sorafenib

Sorafenib, as per standard of care

Intervention Type DRUG

Durvalumab (Regimen 1)

Durvalumab IV (intravenous infusion).

Intervention Type DRUG

Durvalumab (Regimen 2)

Durvalumab IV (intravenous infusion).

Intervention Type DRUG

Other Intervention Names

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MEDI4736

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Los Angeles, California, United States

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Orange, California, United States

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San Francisco, California, United States

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Washington D.C., District of Columbia, United States

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Fort Myers, Florida, United States

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Jacksonville, Florida, United States

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Westwood, Kansas, United States

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Baltimore, Maryland, United States

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Ann Arbor, Michigan, United States

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Rochester, Minnesota, United States

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New York, New York, United States

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Charlotte, North Carolina, United States

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Portland, Oregon, United States

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Pittsburgh, Pennsylvania, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Murray, Utah, United States

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Barretos, , Brazil

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Curitiba, , Brazil

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Florianópolis, , Brazil

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Porto Alegre, , Brazil

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Rio de Janeiro, , Brazil

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São Paulo, , Brazil

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Hamilton, Ontario, Canada

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Kingston, Ontario, Canada

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London, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Sherbrooke, Quebec, Canada

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Beijing, , China

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Changchun, , China

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Changsha, , China

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Chengdu, , China

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Dalian, , China

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Fuzhou, , China

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Guangzhou, , China

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Hangzhou, , China

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Harbin, , China

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Hefei, , China

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Nanchang, , China

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Nanjing, , China

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Nanning, , China

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Shanghai, , China

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Suzhou, , China

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Wuhan, , China

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Xi'an, , China

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Zhengzhou, , China

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Clichy, , France

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Lille, , France

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Marseille, , France

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Montpellier, , France

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Nancy, , France

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Nantes, , France

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Nice, , France

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Pessac, , France

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Poitiers, , France

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Reims, , France

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Rouen, , France

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Saint-Etienne, , France

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Toulouse, , France

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Villejuif, , France

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Aachen, , Germany

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Cologne, , Germany

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Essen, , Germany

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Hanover, , Germany

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Heidelberg, , Germany

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Leipzig, , Germany

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Mainz, , Germany

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München, , Germany

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Tübingen, , Germany

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Ulm, , Germany

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Hong Kong, , Hong Kong

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Bangalore, , India

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Bhubneshwar, , India

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Chennai, , India

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Hubli, , India

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Hyderabad, , India

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Karmsad, , India

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Mumbai, , India

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Nashik, , India

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New Delhi, , India

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Benevento, , Italy

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Meldola, , Italy

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Milan, , Italy

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Napoli, , Italy

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Perugia, , Italy

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Pisa, , Italy

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Roma, , Italy

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Rozzano, , Italy

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Bunkyoku, , Japan

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Chiba, , Japan

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Fukuoka, , Japan

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Hiroshima, , Japan

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Iizuka, , Japan

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Kanazawa, , Japan

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Kōtoku, , Japan

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Kumamoto, , Japan

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Kurume, , Japan

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Matsuyama, , Japan

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Mitakashi, , Japan

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Musashino, , Japan

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Nagoya, , Japan

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Okayama, , Japan

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Osaka, , Japan

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Ōgaki, , Japan

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Ōsaka-sayama, , Japan

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Saga, , Japan

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Sapporo, , Japan

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Shiwa, , Japan

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Suntogun, , Japan

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Tsu, , Japan

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Yokohama, , Japan

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Moscow, , Russia

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Murmansk, , Russia

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Nizhny Novgorod, , Russia

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Novosibirsk, , Russia

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Obninsk, , Russia

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Omsk, , Russia

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Saint Petersburg, , Russia

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Ufa, , Russia

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Ilsan, Gyeonggi-do, South Korea

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Seongnam-si, Gyeonggi-do, South Korea

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Busan, , South Korea

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Daegu, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Barcelona, , Spain

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Madrid, , Spain

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Oviedo, , Spain

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Pamplona Madrid, , Spain

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Santander, , Spain

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Chiayi City, , Taiwan

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Tainan, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

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Bangkok, , Thailand

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Chang Mai, , Thailand

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Khon Kaen, , Thailand

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Phitsanulok, , Thailand

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Songkhla, , Thailand

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Dnipro, , Ukraine

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IvanoFrankivsk, , Ukraine

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Kharkiv, , Ukraine

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Kropyvnitskyi, , Ukraine

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Kyiv, , Ukraine

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Lviv, , Ukraine

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Odesa, , Ukraine

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Uzhhorod, , Ukraine

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Hanoi, , Vietnam

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Hochiminh, , Vietnam

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Countries

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United States Brazil Canada China France Germany Hong Kong India Italy Japan Russia South Korea Spain Taiwan Thailand Ukraine Vietnam

References

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Rimassa 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.

Reference Type DERIVED
PMID: 40222621 (View on PubMed)

Lau 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.

Reference Type DERIVED
PMID: 39089633 (View on PubMed)

Sangro 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.

Reference Type DERIVED
PMID: 38805668 (View on PubMed)

Abou-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.

Reference Type DERIVED
PMID: 38319892 (View on PubMed)

Addendum 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.

Reference Type DERIVED
PMID: 37678916 (View on PubMed)

Patel 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.

Reference Type DERIVED
PMID: 37676259 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2024-512212-21-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2016-005126-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D419CC00002

Identifier Type: -

Identifier Source: org_study_id

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