Monalizumab data from COAST trial presented at ESMO Congress 2021

Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) (“Innate” or the “Company”) today announced that AstraZeneca (LSE/STO/Nasdaq: AZN) presented results from the randomized COAST Phase 2 trial during the European Society for Medical Oncology (ESMO) Congress 2021 on September 17, 2021.

In particular, the results of the interim analysis showed monalizumab in combination with durvalumab improved progression-free survival (PFS) and objective response rate (ORR) compared to durvalumab alone in patients with unresectable, Stage III non-small cell lung cancer (NSCLC) who had not progressed after concurrent chemoradiation therapy (CRT). Monalizumab, Innate’s lead partnered asset, is a potentially first-in-class immune checkpoint inhibitor targeting NKG2A receptors expressed on tumor infiltrating cytotoxic CD8+ T cells and NK cells. 

To read more about the Phase 2 COAST results, please see AstraZeneca’s press release here.

“We’re pleased to see the monalizumab COAST results, particularly the improved clinical outcomes for patients with unresectable, Stage III non-small cell lung cancer,” said Mondher Mahjoubi, Chief Executive Officer of Innate Pharma. “Monalizumab is one of the first checkpoint inhibitors targeting a NK cell receptor, and today’s results further support the role it can play in treating certain cancers by blocking the inhibitory receptor, NKG2A.  We look forward to continuing to invest in NK cell science and further advancing the next wave of scientific innovation at Innate.”  

Based on these results, AstraZeneca informed Innate that it plans to start a registrational study with monalizumab in combination with durvalumab in patients with unresectable, Stage III non-small cell lung cancer (NSCLC).  

Stage III NSCLC:

In 2020, an estimated 2.2 million people were diagnosed with lung cancer worldwide¹. Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.^2,3,4 Stage III NSCLC represents approximately one quarter of NSCLC incidence⁵.

Stage III (locally advanced) NSCLC is commonly divided into three subcategories (IIIA, IIIB and IIIC), defined by how much the cancer has spread locally. In contrast to Stage IV, when cancer has spread (metastasised), the majority of Stage III patients are currently treated with curative intent^2,6.

The majority of Stage III NSCLC patients are diagnosed with unresectable tumours^2,5. 

About Monalizumab: 

Monalizumab 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 reestablish a broad anti-tumor response mediated by NK and T cells, and may enhance the cytotoxic potential of other therapeutic antibodies⁷. 

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

About COAST Trial:

COAST is a Phase 2, multi-arm, randomised trial investigating durvalumab alone or in combination with either monalizumab, an anti-NKG2A monoclonal antibody, or oleclumab, an anti-CD73 monoclonal antibody, in 189 patients with locally advanced, unresectable Stage III NSCLC who had not progressed after concurrent CRT.

COAST is being conducted by AstraZeneca in 82 centers across nine countries in North America, Europe and Asia. The primary endpoint of the trial is ORR as a measure of anti-tumor activity. Secondary endpoints include safety, duration of response, overall survival and PFS. 
 
_{1 World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed September 2021.
2 Provencio M, et al. Inoperable Stage III Non-Small Cell Lung Cancer: Current Treatment and Role Of Vinorelbine. J Thorac Dis. 2011;3:197-204.
3 Cheema PK, et al. Perspectives on Treatment Advances for Stage III Locally Advanced Unresectable Non-Small-Cell Lung Cancer. Curr Oncol. 2019;26(1):37–42.
4 LUNGevity Foundation. Types of Lung Cancer. Available at  https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer. Accessed September 2021.
5 EpiCast Report: NSCLC Epidemiology Forecast to 2025. GlobalData. 2016.
6 ASCO. Cancer.net. Lung Cancer – Non-Small Cell. Available at https://www.cancer.net/cancer-types/lung-cancer/view-all. Accessed September 2021.
7 André et al, Cell 2018}