A phase 1 study of lirilumab (antibody against killer immunoglobulin-like receptor antibody KIR2D; IPH2102) in patients with solid tumors and hematologic malignancies
Metrics: PDF 1698 views | HTML 2965 views | ?
Norbert Vey1,2, Lionel Karlin3, Sophie Sadot-Lebouvier4, Florence Broussais1, Dominique Berton-Rigaud4, Jérôme Rey1, Aude Charbonnier1, Delphine Marie5, Pascale André5, Carine Paturel5, Robert Zerbib5, Jaafar Bennouna4, Gilles Salles3 and Anthony Gonçalves1,2
1Institut Paoli-Calmettes, Marseille, France
2Aix-Marseille Université, Marseille, France
3Centre Hospitalier Universitaire de Lyon Sud, Service d’Hématologie, Pierre Bénite, France
4Institut de Cancérologie de l’Ouest–Site René Gauducheau, St Herblain, France
5Innate Pharma, Marseille, France
Norbert Vey, email: [email protected]
Keywords: monoclonal antibody; cancer immunotherapy; toxicity; natural killer cells
Received: October 05, 2017 Accepted: March 02, 2018 Published: April 03, 2018
Purpose: Anti-KIR monoclonal antibodies (mAbs) can enhance the antitumor responses of natural killer (NK) cells. We evaluated the safety of the anti-KIR2D mAb lirilumab in patients with various cancers.
Experimental design: Thirty-seven patients with hematological malignancies (n = 22) or solid tumors (n = 15) were included in the study. Dose escalation (0.015 to 10 mg/kg) was conducted following a 3 + 3 design. Patients were scheduled to receive four cycles of treatment. In a second (extension) phase 17 patients were treated at 0.015 (n = 9) or 3 mg/kg (n = 8).
Results: No dose-limiting toxicity was recorded. The most frequent lirilumab-related adverse events were pruritus (19%), asthenia (16%), fatigue (14%), infusion-related reaction (14%), and headache (11%), mostly mild or moderate. Pharmacokinetics was dose-dependent and linear, with minimal accumulation resulting from the 4-weekly repeated administrations. Full KIR occupancy (>95%) was achieved with all dosages, and the duration of occupancy was dose-related. No significant changes were observed in the number or distribution of lymphocyte subpopulations, nor was any reduction in the distribution of KIR2D-positive NK cells.
Conclusions: This phase 1 trial demonstrated the satisfactory safety profile of lirilumab up to doses that enable full and sustained blockade of KIR.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.