About this program
IPH4102 is a first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody, designed to selectively destroy cutaneous T-cell lymphomas (CTCL) cancer cells. CTCL is a group of rare cutaneous lymphomas of T lymphocytes with poor prognosis and few therapeutic options at advanced stages.
KIR3DL2 is an inhibitory receptor of the KIR family, expressed by approximately 65% of patients across all CTCL subtypes of the orphan indication of CTCL and expressed by up to 85% of certain agressive CTCL subtypes, in particular, Sézary syndrome and transformed mycosis fungoides. KIR3DL2 has a restricted expression on normal tissues.
IPH4102 was granted orphan drug status in the European Union for the treatment of CTCL.
IPH4102 is currently in Phase I trial for the treatment of CTCL.
Mechanism of action of anti-KIR3DL2
IPH4102 is currently in a Phase I trial for the treatment of relapsed/refractory CTCL.
The Phase I trial is an open label and multicenter study. It is performed in Europe (France, Netherlands, United Kingdom) and in the US. Participating institutions include several hospitals with internationally recognized expertise: the Saint-Louis Hospital (Paris, France), the MD Anderson Cancer Center (Houston, Texas), the Stanford University Medical Center (Stanford, CA), the Ohio State University (Columbus, OH), the Leiden University Medical Center (Leiden, Netherlands), and the Guy’s and St Thomas’ Hospital (London, United Kingdom). 55 patients with advanced CTCL having received at least two prior lines of systemic therapy are expected to be enrolled in two sequential study parts:
- The dose-escalation part has accrued 25 KIR3DL2-positive CTCL patients in 10 dose levels. The objective was to characterize IPH4102 safety profile, identify the Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D); the dose escalation followed an accelerated 3+3 design;
- The cohort expansion part will have 2 cohorts of 15 patients each in 2 CTCL subtypes (transformed mycosis fungoides and Sézary syndrome) receiving IPH4102 at the RP2D until progression.
The primary objective of this trial is to evaluate the safety and tolerability of repeated administrations of single agent IPH4102 in this patient population. The secondary objectives include assessment of the drug’s antitumor activity. Clinical endpoints include global objective response rate, response duration and progression-free survival. A large set of exploratory analyses is aimed at identifying biomarkers of clinical activity.
Encouraging preliminary safety and clinical activity results from the dose-escalation part of the Phase I study in patients with relapsed/refractory CTCL have been presented in a poster at the 3WCCL and ASH annual meeting 2016.
Opinion Leader event chaired by Pr. Youn H. Kim, MD, Professor of Dermatology, Director of the Multidisciplinary Cutaneous Lymphoma Program and Medical Director of the Photopheresis Service at the Stanford Medical Center (New-York, October 2015)
Key Opinion Leader event chaired by Pr Martine Bagot, Head of the Dermatology Department at the Saint-Louis Hospital in Paris and co-discoverer of the target KIR3DL2 (Paris, December 2015) - in French
WARNING: some images may offend the sensibilities
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