Tremelimumab — Drug Monograph

Brand names: Imjudo

Drug class: Checkpoint Inhibitor

Mechanism of Action

Human anti-CTLA-4 IgG2 monoclonal antibody. Blocks CTLA-4 binding to CD80/CD86 on antigen-presenting cells, releasing inhibitory checkpoints on T-cell activation and proliferation. As an IgG2, tremelimumab has reduced Fc receptor binding compared to ipilimumab (IgG1), which may attenuate regulatory T-cell depletion in the tumor microenvironment. In HCC, it is used as a single priming dose (STRIDE regimen) to generate an early immune response, followed by durvalumab maintenance.

FDA Indications

• Hepatocellular carcinoma — unresectable, first-line, in combination with durvalumab (HIMALAYA trial, STRIDE regimen: single 300 mg priming dose of tremelimumab + durvalumab 1500 mg every 4 weeks)

Common Side Effects

• Fatigue
• Diarrhea
• Rash
• Pruritus
• Nausea
• Decreased appetite

Clinical Pearl

The HIMALAYA trial established the STRIDE regimen (single tremelimumab priming dose + durvalumab) as an alternative first-line HCC option. The key innovation is the single priming dose concept — a brief burst of CTLA-4 blockade to prime the immune response, followed by ongoing PD-L1 blockade with durvalumab. OS was non-inferior to sorafenib (HR 0.78) with a more manageable safety profile than dual checkpoint blockade used continuously. Particularly valuable when bevacizumab-containing regimens…

Related Therapies & Mechanisms

• Atezolizumab (Tecentriq) — Checkpoint Inhibitor · HCC
• Durvalumab (Imfinzi) — Checkpoint Inhibitor · HCC
• Nivolumab (Opdivo) — Checkpoint Inhibitor · HCC
• Pembrolizumab (Keytruda) — Checkpoint Inhibitor · HCC