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.
Non-small cell lung cancer is a malignant tumor that develops from the cells lining the walls of the bronchi, bronchial tubes and alveoli. Non-small cell lung cancer accounts for 85-90% of all lung cancers diagnosed each year in France. It has a poor prognosis, with a 5-year survival rate of less than 20% for all stages combined.
| Monalizumab NKG2A In partnership with AstraZeneca | PACIFIC-9: clinical trial 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.
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| Preclinical | Phase 1 | Phase 2 | Phase 3 | |
NeoCOAST-2: clinical study that includes a treatment arm with durvalumab in combination with chemotherapy and monalizumab in resectable, early-stage NSCLC.
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| Preclinical | Phase 1 | Phase 2 | Phase 3 | |
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.
The financial terms of the agreement include potential cash payments up to $1.275 billion to Innate Pharma. To date, Innate Pharma has received $450 million to date under the monalizumab agreement with AstraZeneca.
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