A phase I trial of the anti-inhibitory KIR monoclonal antibody IPH2101 for acute myeloid leukemia (AML) in complete remission
Mené sur 21 patients atteints d'une leucémie myéloïde aiguë en rémission complète (âge médian : 71 ans), cet essai français de phase I évalue un composé appelé IPH201, un anticorps monoclonal inhibiteur du récepteur KIR
IPH2101 is an anti-killer inhibitory receptor (KIR) monoclonal antibody (mAb) that can block KIR mediated inhibition of natural killer (NK) cell to enhance cytotoxicity against AML blasts. We have conducted a phase I study of IPH2101 in elderly patients with AML in first complete remission (CR). Patients received escalating doses (0.0003 to 3 mg/kg) of IPH2101 following a 3+3 design. Safety, toxicity (primary endpoints), pharmacokinetics, progression free, relapse free and overall survival and immunological correlates (secondary endpoints) were evaluated. 23 patients (median age 71 years), were enrolled. Adverse events were mild and transient, mainly an infusion syndrome (fever, chills) and erythema. MTD was not reached although full KIR saturation (>90%) was sustained for more than 2 weeks at 1 and 3 mg/kg. There was a clear correlation between mAb exposure and KIR occupancy. Neither hematologic toxicity nor significant changes in numbers and distribution of lymphocyte subsets, NK cell receptor expression, or in vitro cytotoxicity were seen. At the highest dose levels (0.3, 1 & 3 mg/kg), transient increase in TNF-α and MIP-1β serum concentrations and NK cell CD69 expression were observed. OS and RFS in the present study compared favorably with reports in comparable patient populations. IPH2101 administration is safe and can block KIR for prolonged period of time with limited clinical and immunological side effects. IPH2101-101 study was registered EUDRACT 2005-005298-31.