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

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: Hepatocellular Carcinoma

Treatments: Drug: Sorafenib; Drug: Tremelimumab (Regimen 1); Drug: Durvalumab (Regimen 1); Drug: Durvalumab (Regimen 2); Drug: Tremelimumab (Regimen 2); Drug: Durvalumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03298451

D419CC00002

2024-512212-21-00 (Registry Identifier)

2016-005126-11 (EudraCT Number)

Details and patient eligibility

About

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

Full description

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

Enrollment: 1,324 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

1,324 participants in 4 patient groups

Arm 1

Experimental group

Description:

Durvalumab

Treatment:

Drug: Durvalumab

Arm 2

Experimental group

Description:

Durvalumab in combination with tremelimumab (Regimen 1)

Treatment:

Drug: Durvalumab (Regimen 1)

Drug: Tremelimumab (Regimen 1)

Arm 3

Experimental group

Description:

Durvalumab in combination with tremelimumab (Regimen 2)

Treatment:

Drug: Tremelimumab (Regimen 2)

Drug: Durvalumab (Regimen 2)

Arm 4

Active Comparator group

Description:

Sorafenib

Treatment:

Drug: Sorafenib