Clinical trialPhase 3Liver cancer

Five-year overall survival update from the HIMALAYA study of tremelimumab plus durvalumab in unresectable HCC

J Hepatol · 2025393 STRIDE patients and 389 sorafenib patients (alongside the durvalumab monotherapy group)

Rimassa L, Chan SL, Sangro B, Lau G, Kudo M, Reig M, et al. J Hepatol. 2025. 83:899-908

Study type: Clinical trial
Study name: HIMALAYA
Phase: Phase 3
Design: Updated exploratory analysis of overall survival after 5 years of follow-up in a phase 3 randomised trial (data cut-off: 1 March 2024)
Sample size: 393 STRIDE patients and 389 sorafenib patients (alongside the durvalumab monotherapy group)
Source: J Hepatol · 2025
Trial registration: NCT03298451

In plain words

After 5 years of follow-up, about 1 in 5 (19.6%) of the patients with advanced liver cancer who had received the immunotherapy combination of tremelimumab and durvalumab (STRIDE) were alive, versus 9.4% with the tablet drug sorafenib. No new serious late side effects were seen.

Key results

0.76

Hazard ratio for overall survival (STRIDE vs sorafenib)

95% CI 0.65–0.89

19.6% vs 9.4%

60-month overall survival

All patients

28.7% vs 12.7%

60-month survival in patients with disease control

RECIST version 1.1

50.7% vs 26.3%

60-month survival with tumour shrinkage of more than 25%

21.1% (83 of 393) vs 11.6% (45 of 389)

Extended long-term survivors

Drugs in this study:Sorafenib (Nexavar)Durvalumab (Imfinzi)

Dose and schedule cards

Durvalumab + tremelimumab (STRIDE regimen, HIMALAYA)

Unresectable HCC, no prior systemic therapy (BCLC C, or BCLC B unsuitable for locoregional therapy)Cycle length: Every 28 daysOn the page “Liver cancer” · Advanced hepatocellular carcinoma: first-line

Unresectable HCC, no prior systemic therapy (BCLC C, or BCLC B unsuitable for locoregional therapy)

Drug	Dose	Route	Schedule
Cycle 1, day 1 (once only)
Tremelimumab	300 mg (body weight less than 30 kg: 4 mg/kg)	IV, 60-min infusion	Single dose; before durvalumab on the same day
From cycle 1
Durvalumab	1500 mg (body weight less than 30 kg: 20 mg/kg)	IV, 60-min infusion	Day 1, every 4 weeks

Cycle length: Every 28 days
Duration: Durvalumab until progression or intolerable toxicity

No antiangiogenic agent; in HIMALAYA, endoscopy before enrollment was not mandatory, but patients with a history of variceal bleeding or at high risk of it required appropriate endoscopic treatment.

Durvalumab monotherapy (1500 mg IV every 4 weeks) was non-inferior to sorafenib in the same trial.

On the page “Liver cancer” · Advanced hepatocellular carcinoma: first-line

STRIDE

Advanced liver cancer, first line, Child-Pugh ACycle length: Every 4 weeksOn the page “Durvalumab and tremelimumab in liver cancer (STRIDE)”

Advanced liver cancer, first line, Child-Pugh A

Drug	Dose	Route	Schedule
First dose
Tremelimumab	300 mg	IV	Day 1 (once)
Durvalumab	1500 mg	IV	Day 1, then every 4 weeks

Cycle length: Every 4 weeks
Duration: Until progression

As in HIMALAYA.

Dose source:.

On the page “Durvalumab and tremelimumab in liver cancer (STRIDE)”

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1STRIDE (tremelimumab + durvalumab)

Tremelimumab 300 mg IV infusion, a single dose only on day 1 of cycle 1, with durvalumab 1500 mg IV on the same day (tremelimumab before durvalumab); then durvalumab 1500 mg IV every 4 weeks until disease progression or unacceptable toxicity (continuation beyond progression was allowed in clinically stable patients with clinical benefit).

According to the FDA label: for body weight below 30 kg, tremelimumab 4 mg/kg once + durvalumab 20 mg/kg, then durvalumab 20 mg/kg every 4 weeks; tremelimumab is infused over 60 minutes.

2Durvalumab (monotherapy)

Durvalumab 1500 mg IV infusion every 4 weeks until disease progression or unacceptable toxicity.

3Sorafenib

Sorafenib 400 mg orally twice daily until disease progression or unacceptable toxicity.

Source of the regimen details: This paper is a follow-up report and gives no doses; the regimen is that of the original HIMALAYA trial: abstract of the original paper (NEJM Evid 2022) and FDA labels for Imjudo and Imfinzi (openFDA/DailyMed, dosing and HIMALAYA study sections); ClinicalTrials.gov NCT03298451 (eligibility criteria)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with histologically confirmed unresectable HCC and no prior systemic therapy, BCLC stage C or B (not eligible for locoregional therapy), with Child-Pugh A and ECOG 0 or 1 (ClinicalTrials.gov). Exclusion criteria: hepatic encephalopathy in the past 12 months, clinically significant ascites (according to the FDA label: ascites requiring non-pharmacological intervention in the past 6 months), tumour thrombosis of the main portal vein trunk, active or prior gastrointestinal bleeding in the past 12 months, HBV and HCV or HBV and HDV co-infection, and active or prior autoimmune disease. According to the FDA label, endoscopy before enrolment was not mandatory, but adequate endoscopic treatment was required in patients with a history of variceal bleeding or at high risk of it.

Endpoints

Overall survival, depth of response and serious adverse events; description of extended long-term survivors (48 months or more after randomisation).

Safety and side effects

No late serious treatment-related adverse events were reported for STRIDE.

Clinical significance and place in guidelines

The longest survival data for an immunotherapy combination in HCC; it confirms the durability of the STRIDE benefit. The ESMO guideline (Asian adapted version 2026) recommends durvalumab–tremelimumab first-line at level I, A.

Limitations

Exploratory analysis; the analysis by tumour response is defined after randomisation and is open to bias.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.