Monalizumab (IPH2201) is a potentially first-in-class immune checkpoint inhibitor targeting NKG2A receptors expressed on tumor infiltrating cytotoxic CD8+ T cells and NK cells.

NKG2A is an inhibitory checkpoint receptor for HLA-E. By expressing HLA-E, cancer cells can protect themselves from killing by NKG2A+ immune cells. HLA-E is frequently overexpressed on cancer cells of many solid tumors and hematological malignancies. Monalizumab may re-establish a broad anti-tumor response mediated by NK and T cells, and may enhance the cytotoxic potential of other therapeutic antibodies (André et al, Cell 2018).

Mechanism of action

Monalizumab is a blocking antibody that prevents the inhibition of CD8+ T cells and NK cell by tumor cells expressing HLA-E. By acting simultaneously on innate and adaptive immunity, monalizumab may re-establish a broad anti-tumor response.

Mechanism of action of monalizumab


Monalizumab is being investigated in monotherapy and in combination with other agents in various indications. Current trials include:

  • INTERLINK-1 is a global, multi-center, randomized, double-blind Phase 3 study of monalizumab and cetuximab vs. placebo and cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma of the head and neck (R/M SCCHN) who have been previously treated with platinum-based chemotherapy and PD-(L)1 inhibitors.  -  AstraZeneca and Innate elected to advance this program directly to a Phase 3 study based on the Phase 1b/2 results and the unmet need in the IO-pretreated population. Learn more about INTERLINK-1.
  • A Phase 2 combination clinical trial with cetuximab and durvalumab, an anti-PD-L1 immune checkpoint inhibitor developed by AstraZeneca, in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN)
  • Phase 1/2 clinical trials in combination with durvalumab in solid tumors. 

See the full list of ongoing trials with monalizumab on

In April 2015, the Company signed a co development and commercialization agreement with AstraZeneca to accelerate and broaden the development of monalizumab. In 2018, AstraZeneca obtained full oncology rights to monalizumab.

Learn more about Innate’s partnership with AstraZeneca

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