Published in:
01-10-2010 | Original Article
Phase I study of bromohydrin pyrophosphate (BrHPP, IPH 1101), a Vγ9Vδ2 T lymphocyte agonist in patients with solid tumors
Authors:
Jaafar Bennouna, Vincent Levy, Hélène Sicard, Hélène Senellart, Marie Audrain, Sandrine Hiret, Frédéric Rolland, Heriberto Bruzzoni-Giovanelli, Marie Rimbert, Céline Galéa, Jérome Tiollier, Fabien Calvo
Published in:
Cancer Immunology, Immunotherapy
|
Issue 10/2010
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Abstract
Purpose
Vγ9Vδ2 (γδ) T lymphocytes, a critical peripheral blood lymphocyte subset, are directly cytotoxic against many solid and hematologic tumor types. Vγ9Vδ2 T lymphocytes can be selectively expanded in vivo with BrHPP (IPH1101) and IL-2. The present phase I trial was conducted with the aim of determining the maximum-tolerated dose (MTD) and safety of IPH1101 combined with a low dose of IL-2 in patients with solid tumors.
Experimental design
A 1-h intravenous infusion of IPH11 was administered alone at cycle 1, combined with a low dose of SC IL-2 (1 MIU/M2 d1 to d7) in the subsequent cycles (day 1 every 3 weeks). The dose of IPH1101 was escalated from 200 to 1,800 mg/m2.
Results
As much as 28 patients with solid tumors underwent a total of 109 treatment cycles. Pharmacodynamics data demonstrate that γδ T lymphocyte amplification in humans requires the co-administration of IL-2 and is dependent on IPH 1101 dose. Dose-limiting toxicity occurred in two patients at a dose of 1,800 mg/m2: one grade 3 fever (1 patient) and one grade 3 hypotension (1 patient) suggesting cytokine release syndrome immediately following the first infusion. At lower doses the treatment was well tolerated; the most frequent adverse events were mild fever, chills and abdominal pain, without exacerbation in the IL-2 combined cycles.
Conclusion
IPH1101 in combination with SC low-dose IL-2 is safe, well tolerated and induces a potent γδ T lymphocyte expansion in patients. Its clinical activity will be evaluated in phase II clinical trials.