AstraZeneca's Imfinzi (durvalumab) plus Imjudo (tremelimumab-actl) has demonstrated unprecedented overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC), with approximately one in five patients surviving five years in the Phase III HIMALAYA trial. The STRIDE regimen, which includes a single priming dose of Imjudo 300mg added to Imfinzi 1500mg, followed by Imfinzi every four weeks, has shown a significant improvement in long-term survival compared to sorafenib, a standard-of-care multi-kinase inhibitor.
The HIMALAYA trial included 1,324 patients with unresectable, advanced HCC who had not received prior systemic therapy and were not eligible for locoregional therapy. The trial was conducted across 181 centers in 16 countries, including the US, Canada, Europe, South America, and Asia. The primary endpoint was OS for the combination versus sorafenib, with key secondary endpoints including OS for Imfinzi versus sorafenib, objective response rate, and progression-free survival (PFS) for the combination and for Imfinzi alone.
Safety and Tolerability
The safety profile of the STRIDE regimen was consistent with the known profiles of each medicine, and no new safety signals were observed with longer follow-up. Serious treatment-related adverse events, defined as Grade 3 or 4 and including death, were experienced by 17.5% of patients treated with the STRIDE regimen versus 9.9% of patients treated with sorafenib, with no new events occurring after the primary analysis for STRIDE.
Mechanism of Action
Imfinzi is a human monoclonal antibody that binds to the PD-L1 protein, blocking its interaction with PD-1 and CD80 proteins. This mechanism counters the tumor’s immune-evading tactics and releases the inhibition of immune responses. Imjudo, another human monoclonal antibody, targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), contributing to T-cell activation and priming the immune response to cancer.
Current Approvals and Indications
Imfinzi in combination with Imjudo is approved for the treatment of adults with advanced or unresectable HCC in the US, EU (in the 1st-line setting), Japan, and several other countries. Imfinzi monotherapy is also approved in Japan in this setting. Additionally, Imfinzi has approvals for unresectable Stage III non-small cell lung cancer (NSCLC), extensive-stage small cell lung cancer (SCLC), locally advanced or metastatic biliary tract cancer (BTC), and mismatch repair deficient endometrial cancer.
Liver Cancer Context
Liver cancer, with HCC being the most common type, is the third-leading cause of cancer death globally, with nearly 900,000 new diagnoses each year. Advanced-stage HCC has a poor prognosis, with a five-year survival rate of only 7%. The unique immune environment of liver cancer makes it a prime target for immunotherapeutic interventions.
