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IPH4102: Potential Treatment for Cutaneous T-Cell Lymphoma

T-cell lymphoma.

Researchers report that IPH4102, a first-in-class monoclonal antibody that targets killer cell immunoglobulin-like receptor 3DL2 (KIR3DL2), shows promising activity in relapsed or refractory cutaneous T-cell lymphoma (CTCL), a rare cancer that affects the skin. A cell surface protein, KIR3DL2 is expressed particularly strongly in patients with a form of CTCL called Sézary syndrome, which is an aggressive blood cancer.

This international, first-in-human, open-label phase 1 clinical trial (NCT02593045), published in The Lancet Oncology, enrolled 44 adult patients with histologically confirmed relapsed or refractory primary CTCL, an Eastern Cooperative Oncology group performance score of 2 or less, and two or more prior systemic therapies. Ten dose levels of IPH4102, ranging from 0.0001 mg/kg to 10 mg/kg, were intravenously administered to the patients.

After a median follow-up of 14.1 months, IPH4102 produced an overall response in 36.4% of patients. Treatment-related adverse events included peripheral edema (27%) and fatigue (20%), both of which were only grade 1 to 2. Lymphopenia, the most common grade 3 or worse side effect, occurred in 7% of patients. The investigators also found that 750 mg of IPH4102 should be the recommended dose.

"IPH4102 is safe and shows encouraging clinical activity in patients with relapsed or refractory CTCL, particularly those with Sézary syndrome," conclude the authors of the study. "If confirmed in future trials, IPH4102 could become a novel treatment option for these patients. A multi-cohort, phase 2 trial (TELLOMAK) is underway to confirm the activity in patients with Sézary syndrome and explore the role of IPH4102 in other subtypes of T-cell lymphomas that express KIR3DL2."

For More Information

Bagot M, Porcu P, Marie-Cardine A, et al (2019). IPH4102, a first-in-class anti-KIR3DL2 monoclonal antibody, in patients with relapsed or refractory cutaneous T-cell lymphoma: an international, first-in-human, open-label, phase 1 trial. Lancet Oncol. [Epub ahead of print] DOI:10.1016/S1470-2045(19)30320-1

Clinicaltrials.gov (2019). Study of IPH4102 in patients with relapsed/refractory cutaneous T-cell lymphomas (CTCL). NLM Identifier: NCT02593045.

Image Courtesy of Creative Commons. Licensed Under CC BY-SA 3.0

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