About this program

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 in the 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.

AstraZeneca obtained full oncology rights to monalizumab in October 2018 through a co-development and commercialization agreement initiated in 2015. The ongoing Phase II development for monalizumab is focused on investigating monalizumab in various combination strategies in different malignancies.

Mechanism of action of anti-NKG2A

Monalizumab is the only checkpoint inhibitor developed to date that is capable of acting simultaneously on T and NK cells, which could provide a more effective immune response. It also acts on tumor-infiltrating immune cells, i.e. a targeted action which could translate into a favorable benefit / risk profile.

 

On April 24 2015, the Company signed a co‑development and commercialization agreement with AstraZeneca to accelerate and broaden the development of monalizumab.

The financial terms of the agreement include potential cash payments of up to $1.275 billion to Innate Pharma. The Company has already received $350 million, and the next payment due by AstraZeneca is $100 million upon dosing of the first patient in a first Phase III clinical trial. AstraZeneca will book all sales and will pay Innate low double-digit to mid-teen percentage royalties on net sales worldwide except in Europe where Innate Pharma will receive 50% share of the profits and losses in the territory. Innate will co-fund 30% of the costs of the Phase III development program of monalizumab with a pre-agreed limitation of Innate’s financial commitment.

A broad exploratory clinical program is ongoing, investigating monalizumab in monotherapy and in combination with other agents in various indication.

The development plan includes:

 

See the full list of ongoing trials with monalizumab on clinicaltrials.gov.

Monalizumab

Head and Neck, squamous cell carcinoma

Colon carcinoma

Documents: 

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ASCO 2020: Combination of monalizumab & cetuximab in patients with R/MSCCHN cancer previously treated...435.05 KB
ESMO 19: Durvalumab plus monalizumab, mFOLFOX6, and bevacizumab in patients with metastatic MSS CRC353.38 KB
ESMO 19: Monalizumab in combination with cetuximab in patients with R/M SCCHN... 1-year survival data354.43 KB
SITC 2018: Monalizumab in combination with cetuximab in R/M SCCHN: Clinical results and preliminary biomarker analyses1.41 MB
ESMO 2018: Phase II study of monalizumab in combination with cetuximab in R/M SCCHN1.23 MB
ESMO 2018: Changes in the innate immune system as early events in cancer2.24 MB
ECI 2018: Anti-NKG2A mAb is a checkpoint inhibitor that promotes anti-tumor immunity by unleashing both T and NK cells2.32 MB
ASCO 2018: First-in-Human dose escalation of monalizumab plus durvalumab with expansion in patients with MSS colorectal cancer175.32 KB
AACR 2018: Phase II of monalizumab with cetuximab in previously treated R/M SCCHN: preliminary assessment of safety and efficacy1.37 MB
AACR 2018: NKG2A immune checkpoint blockade potentiates cetuximab induced ADCC in head and neck cancer preclinical model1.13 MB
AACR 2018: Combination of monalizumab and durvalumab as a potent immunotherapy treatment for human solid cancers350.81 KB
ITOC5 2018: Next generation immunotherapies: NK cells and other targets1.95 MB
CRI-CIMT-EATI-AACR ICI 2017: Combined blockade of PD-L1 and NKG2A enhances anti-tumor CD8+ T cell response1.16 MB
AACR 2017: Safety of monalizumab in combination with cetuximab: a Phase Ib/II study in R/M SCCHN339.78 KB
AACR 2017: NKG2A checkpoint receptor expression on tumor-infiltrating CD8+ T cells restrains efficacy of immunotherapy 1.51 MB
ENA 2016: Dose ranging study of monalizumab in patients with gynecologic malignancies: A trial of the CCTG911.89 KB
SITC 2016: NK, T cells and IFN-gamma are required for the anti-tumor efficacy of combination-treatment with NKG2A & PD1/PDL1 IC720.01 KB
AACR 2016: NKG2A immune checkpoint blockade enhances the anti-tumor efficacy of PD-1/PD-L1 inhibitors in a preclinical model239.61 KB
Presentation at the 13th TAT Congress: rationale and protocol of the Phase I/II trial of IPH2201 in ovarian cancer1.66 MB