Oncotarget

Research Papers:

A phase 1 study of lirilumab (antibody against killer immunoglobulin-like receptor antibody KIR2D; IPH2102) in patients with solid tumors and hematologic malignancies

Norbert Vey _, Lionel Karlin, Sophie Sadot-Lebouvier, Florence Broussais, Dominique Berton-Rigaud, Jérôme Rey, Aude Charbonnier, Delphine Marie, Pascale André, Carine Paturel, Robert Zerbib, Jaafar Bennouna, Gilles Salles and Anthony Gonçalves

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Oncotarget. 2018; 9:17675-17688. https://doi.org/10.18632/oncotarget.24832

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Abstract

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

Correspondence to:

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

ABSTRACT

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.


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