Unresectable Hepatocellular Carcinoma: Dual Immune Checkpoint Blockade with STRIDE Regimen

HIMALAYA Phase III Trial: Unprecedented Survival Benefit

• January 18, 2022
• Reading time: 2 minutes

On January 18, 2022, AstraZeneca announced results from the HIMALAYA Phase III randomized clinical trial evaluating the efficacy and safety of combined immune checkpoint blockade as first-line treatment for unresectable hepatocellular carcinoma patients ineligible for locoregional therapy.

Trial Design and Treatment Arms

HIMALAYA was an international, multi-institutional, randomized Phase III open-label study enrolling 1,171 treatment-naive patients with unresectable hepatocellular carcinoma ineligible for locoregional therapy, randomized into three arms:

Arm 1 - Imfinzi (Durvalumab) Monotherapy:

• Durvalumab 1,500 mg IV every 4 weeks
• N=389 patients

Arm 2 - STRIDE Regimen (Durvalumab Plus Tremelimumab):

• Durvalumab 1,500 mg IV plus Tremelimumab 300 mg IV on Day 1
• Followed by durvalumab monotherapy continuing every 4 weeks
• N=393 patients

Arm 3 - Sorafenib Control:

• Sorafenib tyrosine kinase inhibitor
• N=389 patients

Primary endpoint: overall survival comparing STRIDE vs Sorafenib

Secondary endpoints: overall survival across all groups, objective response rate, progression-free survival

Primary Efficacy Results

Overall Survival - STRIDE vs Sorafenib:

• STRIDE group: 16.4 months median
• Sorafenib group: 13.8 months median
• 22% reduction in mortality risk with STRIDE regimen

2-Year Overall Survival Rates:

• STRIDE: 40.5%
• Durvalumab monotherapy: 39.6%
• Sorafenib: 32.6%

3-Year Overall Survival Rates:

• STRIDE: 30.7%
• Durvalumab monotherapy: 24.7%
• Sorafenib: 20.2%

Secondary Efficacy Outcomes

Objective Response Rate:

• STRIDE: 20.1%
• Durvalumab monotherapy: 17.0%
• Sorafenib: 5.1%

Median Duration of Response:

• STRIDE: 22.3 months
• Durvalumab monotherapy: 16.8 months
• Sorafenib: 18.4 months

Safety and Tolerability

Grade 3-4 Adverse Events:

• STRIDE: 25.8%
• Durvalumab monotherapy: 12.9%
• Sorafenib: 36.9%

Hepatology-Related Adverse Events:

• STRIDE: 5.9%
• Durvalumab monotherapy: 5.2%
• Sorafenib: 4.5%

Treatment Discontinuation Due to Adverse Events:

• STRIDE: 8.2%
• Durvalumab monotherapy: 4.1%
• Sorafenib: 11%

Safety profiles of STRIDE and durvalumab monotherapy were consistent with prior clinical experience. No novel unexpected adverse events were identified.

Clinical Conclusions

According to Ghassan Abou-Alfa, MD, principal investigator from Memorial Sloan Kettering Cancer Center:

"Treatment-naive, unresectable hepatocellular carcinoma patients ineligible for locoregional therapy have historically demonstrated poor prognosis, necessitating novel therapeutic approaches. The HIMALAYA trial demonstrates that STRIDE combination immunotherapy delivers substantially improved 3-year overall survival rates with a favorable safety profile compared to sorafenib. These results support STRIDE as a potential new first-line treatment paradigm for this patient population with otherwise limited therapeutic options."

Data Source

https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-plus-tremelimumab-unprecedented-survival-1st-line-unresectable-liver-cancer.html

Related Hepatocellular Carcinoma Treatment Options

• Immunotherapy
• Clinical Trial Therapeutics
  • (Lung Cancer) Topotecan and Topotecan Plus Berzosertib Phase II Trial Results
  • (Lung Cancer) HER2-Mutant Non-Small Cell Lung Cancer Treatment with Enhertu
  • (Lung Cancer) Anti-B7-H3 Antibody DS-7300 Clinical Efficacy

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