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Bending the Curve Trial by Trial
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HIMALAYA

Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma

Phase 3N = 1,171NCT03298451

Population
Patients with unresectable hepatocellular carcinoma and no previous systemic treatment
Design
Global, open-label phase 3 trial; patients with unresectable hepatocellular carcinoma and no previous systemic treatment were randomly assigned to one of three regimens: a single dose of tremelimumab plus durvalumab every 4 weeks (STRIDE), durvalumab alone, or sorafenib. The primary objective was overall survival for STRIDE versus sorafenib; non-inferiority of durvalumab versus sorafenib was a secondary objective.
Primary endpoint
OS
Arms
  • STRIDE (tremelimumab plus durvalumab) (experimental, n = 393): Tremelimumab 300 mg (one dose) plus durvalumab 1500 mg every 4 weeks
  • Durvalumab (experimental, n = 389): Durvalumab 1500 mg every 4 weeks
  • Sorafenib (control, n = 389): Sorafenib 400 mg twice daily
People
Abou-Alfa GK
OSHR 0.78Δ median OS+2.66 monthsΔ 36-month OS+10.5 pointsOSHR 0.86OSHR 0.78 (95% CI 0.67–0.92)Δ 36-month OS+10.9 points
Show the numbers
Results reported for HIMALAYA
EndpointAnalysisSTRIDE (tremelimumab plus durvalumab) / DurvalumabSorafenibEffect
OSRandomly assigned patients (STRIDE comparison is against sorafenib)primaryAbou-Alfa 2022median 16.43 months (14.16–19.58); 30.7% at 3 ymedian 13.77 months (12.25–16.13); 20.2% at 3 yHR 0.78P=0.0035Hazard ratio for STRIDE versus sorafenib; the abstract gives a 96.02% confidence interval of 0.65 to 0.93 (not a 95% interval). The abstract does not give confidence intervals for the 36-month survival rates.
OSRandomly assigned patients (durvalumab versus sorafenib)primaryAbou-Alfa 2022——HR 0.86Hazard ratio for durvalumab versus sorafenib; the abstract gives a 95.67% confidence interval of 0.73 to 1.03 and a non-inferiority margin of 1.08. Non-inferiority was a secondary objective.
OSRandomly assigned patients (STRIDE versus sorafenib; abstract does not state ITT)long term-updateSangro 202430.7% at 3 y; 25.2% at 4 y19.8% at 3 y; 15.1% at 4 yHR 0.78 (95% CI 0.67–0.92)Four-year overall survival update, data cut-off 23 January 2023; median follow-up 49.12 months (STRIDE) and 47.31 months (sorafenib). The 36-month sorafenib rate here (19.8%) differs from the primary report (20.2%).
OSRandomly assigned patients (STRIDE versus sorafenib; abstract does not state ITT)exploratoryRimassa 202519.6% at 5 y9.4% at 5 yHR 0.76 (95% CI 0.65–0.89)Updated exploratory analysis of overall survival after 5 years, data cut-off 1 March 2024; median follow-up 62.49 months (STRIDE) and 59.86 months (sorafenib).
Results reported for HIMALAYA
EndpointAnalysisSTRIDE (tremelimumab plus durvalumab) / DurvalumabSorafenibEffect
OSRandomly assigned patients (STRIDE comparison is against sorafenib)primaryAbou-Alfa 2022median 16.43 months (14.16–19.58); 30.7% at 3 ymedian 13.77 months (12.25–16.13); 20.2% at 3 yHR 0.78P=0.0035Hazard ratio for STRIDE versus sorafenib; the abstract gives a 96.02% confidence interval of 0.65 to 0.93 (not a 95% interval). The abstract does not give confidence intervals for the 36-month survival rates.
OSRandomly assigned patients (durvalumab versus sorafenib)primaryAbou-Alfa 2022——HR 0.86Hazard ratio for durvalumab versus sorafenib; the abstract gives a 95.67% confidence interval of 0.73 to 1.03 and a non-inferiority margin of 1.08. Non-inferiority was a secondary objective.
OSRandomly assigned patients (STRIDE versus sorafenib; abstract does not state ITT)long term-updateSangro 202430.7% at 3 y; 25.2% at 4 y19.8% at 3 y; 15.1% at 4 yHR 0.78 (95% CI 0.67–0.92)Four-year overall survival update, data cut-off 23 January 2023; median follow-up 49.12 months (STRIDE) and 47.31 months (sorafenib). The 36-month sorafenib rate here (19.8%) differs from the primary report (20.2%).
OSRandomly assigned patients (STRIDE versus sorafenib; abstract does not state ITT)exploratoryRimassa 202519.6% at 5 y9.4% at 5 yHR 0.76 (95% CI 0.65–0.89)Updated exploratory analysis of overall survival after 5 years, data cut-off 1 March 2024; median follow-up 62.49 months (STRIDE) and 59.86 months (sorafenib).
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.780.67–0.92
OS0.760.65–0.89
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%010203040Months (modelled)
  • STRIDE (tremelimumab plus durvalumab) (experimental)
  • Durvalumab (experimental)
  • Sorafenib (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsSTRIDE (tremelimumab plus durvalumab)DurvalumabSorafenib
0100.0%100.0%100.0%
1065.6%65.8%60.4%
2141.2%41.5%34.7%
3127.0%27.3%21.0%
4117.7%18.0%12.7%
Illustrative — modelled from reported values, not trial data. OS, long term-update.
0%25%50%75%100%01020304050Months (modelled)
  • STRIDE (tremelimumab plus durvalumab) (experimental)
  • Sorafenib (control)
Data table (modelled values)
MonthsSTRIDE (tremelimumab plus durvalumab)Sorafenib
0100.0%100.0%
1372.8%67.7%
2646.1%36.3%
3928.1%17.4%
5225.2%15.1%
Primary publication: Abou-Alfa GK, Lau G, Kudo M, Chan SL, Kelley RK, Furuse J, et al. Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma. NEJM Evid. 2022;1(8):EVIDoa2100070. PubMedDOI

Appears in

Sources

  1. Abou-Alfa GK, Lau G, Kudo M, Chan SL, Kelley RK, Furuse J, et al. Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma. NEJM Evid. 2022;1(8):EVIDoa2100070.

    PubMedDOI

  2. Sangro B, Chan SL, Kelley RK, Lau G, Kudo M, Sukeepaisarnjaroen W, et al. Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. Ann Oncol. 2024;35(5):448-457.

    PubMedDOI

  3. Rimassa L, Chan SL, Sangro B, Lau G, Kudo M, Reig M, et al. Five-year overall survival update from the HIMALAYA study of tremelimumab plus durvalumab in unresectable HCC. J Hepatol. 2025;83(4):899-908.

    PubMedDOI