Correlations were observed with both the patients’ monocyte (i.e. the primary target cell for IMP321) count before treatment and the degree of activation of monocytes during treatment. The study was an open-label fixed-dose-escalation trial carried out in three cancer centres in the Paris region.
Metastatic breast carcinoma patients were administered one dose of IMP321 subcutaneously every two weeks for a total of 24 weeks (12 injections). IMP321 induced a sustained increase in the number and activation of APC (monocytes and dendritic cells) and an increase in the percentage of NK and long-lived cytotoxic effector-memory CD8 T cells.
Clinical benefit was observed for 90 per cent of patients, with only three progressors at six months. In addition, the objective tumour response rate of 50 per cent compared favourably to the 25 per cent rate reported in the historical control group.
IMP321 is a recombinant soluble LAG-3Ig fusion protein that binds to MHC class II with high avidity and mediates APC and then antigen-experienced memory CD8+ T cell activation.
‘We now have the results required to go forward to a pivotal trial,’ said Frédéric Triebel, Scientific and Medical Director of Immutep. ‘This form of chemo-immunotherapy should be applicable to many chemotherapies. For example, it is now being tested in the USA in association with gemcitabine in pancreatic cancer.’
‘Partnering discussions are in progress to carry out the phase IIb/III pivotal trial leading to Conditional Marketing Authorisation in Europe and further trials in other cancers and with other chemotherapies,’ added John Hawken, CEO.
Further reading
Brignone, C et al. (2010). First-line chemoimmunotherapy in metastatic breast carcinoma: combination of paclitaxel and IMP321 (LAG-3Ig) enhances immune responses and antitumor activity. Journal of Translational Medicine 8, 71