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.
Monalizumab is being investigated in monotherapy and in combination with other agents in various indications. Main trials include:
- PACIFIC-9: AstraZeneca initiated a Phase 3 clinical trial, PACIFIC-9, evaluating durvalumab (anti-PD-L1) in combination with monalizumab (anti-NKG2A) or AstraZeneca’s oleclumab (anti-CD73) in patients with unresectable, Stage III non small cell lung cancer (NSCLC) who have not progressed following definitive platinum-based concurrent chemoradiation therapy. Learn more about PACIFIC-9.
- A Phase 2 clinical study, NeoCOAST-2, that includes a treatment arm with durvalumab in combination with chemotherapy and monalizumab in resectable, early-stage NSCLC.
See the full list of ongoing trials with monalizumab in the Clinical Trials Appendix.
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.