Back to Search
Start Over
A phase 1 trial of the anti-KIR antibody IPH2101 in patients with relapsed/refractory multiple myeloma.
- Source :
-
Blood [Blood] 2012 Nov 22; Vol. 120 (22), pp. 4324-33. Date of Electronic Publication: 2012 Oct 01. - Publication Year :
- 2012
-
Abstract
- Natural killer (NK) cells elicit cytotoxicity against multiple myeloma (MM); however, MM cells express HLA class I molecules as ligands to NK cell inhibitory killer immunoglobulin-like receptors (KIRs) as a means of immunoevasion. KIR-ligand mismatch may improve outcomes in allogeneic transplantation for MM. Extrapolating on this concept, we conducted a phase 1 trial of IPH2101, an anti-KIR antibody, in patients with relapsed/refractory MM. IPH2101 was administered intravenously every 28 days in 7 dose-escalated cohorts (0.0003-3 mg/kg) for up to 4 cycles. Pharmacokinetic, pharmacodynamic, and correlative immunologic studies were completed. A total of 32 patients were enrolled. The biologic endpoint of full KIR2D occupancy across the dosing cycle was achieved without dose-limiting toxicity or maximally tolerated dose. One severe adverse event was noted. Pharmacokinetic and pharmacodynamic findings approximated preclinical predictions, and IPH2101 enhanced ex vivo patient-derived NK cell cytotoxicity against MM. No objective responses were seen. No evidence of autoimmunity was observed. These findings suggest that IPH2101 is safe and tolerable at doses that achieve full inhibitory KIR saturation, and this approach warrants further development in MM. This trial was registered at www.clinicaltrials.gov as #NCT00552396.
- Subjects :
- Administration, Intravenous
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal administration & dosage
Antibodies, Monoclonal adverse effects
Antibodies, Monoclonal, Humanized
Cytotoxicity, Immunologic drug effects
Cytotoxicity, Immunologic immunology
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm drug effects
Drug Resistance, Neoplasm immunology
Female
Humans
Immunotherapy methods
Killer Cells, Natural drug effects
Killer Cells, Natural immunology
Male
Middle Aged
Multiple Myeloma immunology
Receptors, KIR antagonists & inhibitors
Receptors, KIR immunology
Recurrence
Antibodies, Monoclonal therapeutic use
Multiple Myeloma therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 120
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 23033266
- Full Text :
- https://doi.org/10.1182/blood-2012-06-438028