About this program
IPH5401 is a first-in-class therapeutic antibody that specifically binds and blocks C5a receptors (C5aR) expressed on subsets of myeloid-derived suppressor cells (MDSC) and neutrophils. Part of the innate immune system, these types of cells promote tumor growth by secreting inflammatory and angiogenic factors. They potently suppress T and NK cells and hamper the activities of PD-1 checkpoint blockers.
C5a, a factor in the complement cascade, is often overexpressed in tumors, where it attracts and activates MDSC and neutrophils in the tumor microenvironment.
IPH5401 is a fully human antibody that blocks the binding of C5a to C5aR, thereby reducing the accumulation and activation of MDSC and neutrophils in tumors. Treatment with IPH5401 may unleash anti-tumor activities of T cells and NK cells. Preclinical experiments support development of IPH5401 as single agent and in combination with PD-1 checkpoint blockers or other cancer immunotherapies.
Innate Pharma acquired full worldwide exclusive rights to develop and commercialize the anti-C5aR antibody from Novo Nordisk A/S in July 2017.
Mechanism of action of IPH5401
In January 2018, Innate Pharma and AstraZeneca entered into a clinical trial collaboration to evaluate the safety and efficacy of the combination of IPH5401 and durvalumab (anti-PD-L1) in a Phase I/II study for patients with selected solid tumors (NSCLC and HCC) based on C5aR expression.
The trial, called STELLAR-001*, started in September 2018.
The Phase I part of the trial is expected to establish a recommended dose regimen of IPH5401 in combination with durvalumab in selected solid tumors, and the Phase II part will assess the safety and efficacy of the combination in patients with NSCLC or HCC (about 40 patients per indication).
Clinical trial sites are located in France and the US. For more information on the STELLAR-001 clinical study (NCT03665129), please visit clinicaltrials.gov.
The Anti-C5aR had a favorable safety profile in single & multi-dose, placebo controlled Phase I trials in rheumatoid arthritis led by Novo Nordisk A/S.
STELLAR = SelecTivE bLocking of compLement receptor C5AR to boost immune response and improve cancer outcomes
Pio et al, 2019. Complementing the Cancer-Immunity Cycle Frontiers in Immunology Medler et al, 2018. Complement C5a Fosters Squamous Carcinogenesis and Limits T Cell Response to Chemotherapy Cancer Cell Ajona et al, 2017. A Combined PD-1/C5a Blockade Synergistically Protects against Lung Cancer Growth and Metastasis Cancer discovery Liang et al, 2016. The Complex Role of Neutrophils in Tumor Angiogenesis and Metastasis Cancer Immunol Res. Hwu et al, 2016. Complementing T-cell Function: An Inhibitory Role of the Complement System in T-cell-Mediated Antitumor Immunity Cancer discovery Wang et al, 2016. Autocrine Complement Inhibits IL10-Dependent T-cell-Mediated Antitumor Immunity to Promote Tumor Progression Cancer discovery Janelle V et al, 2014. Role of the complement system in NK cell-mediated antitumor T-cell responses Oncoimmunology Kim et al, 2014. Eradication of metastatic mouse cancers resistant to immune checkpoint blockade by suppression of myeloid-derived cells PNAS Corrales et al, 2012. Anaphylatoxin C5a creates a favorable microenvironment for lung cancer progression J Immunol Markiewski et al, 2008. Modulation of the antitumor immune response by complement Nat Immunol.