About this program
IPH4102 is a first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody, designed for treatment of cutaneous T-cell lymphomas (CTCL), an orphan disease. 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 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 and in the United States 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 were 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 safety and clinical activity data of all dose levels were presented at the EORTC CLTF meeting in October 2017.
- The cohort expansion part is accruing 2 cohorts of 15 patients each in 2 CTCL subtypes (Sézary syndrome and transformed mycosis fungoides) receiving IPH4102 at the RP2D of 750 mg (fixed dose equivalent to 10 mg/kg) 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. Exploratory analyses are aimed at identifying biomarkers of clinical activity.
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
Battistella M et al, 2016. KIR3DL2 (CD158k) is a potential therapeutic target in primary cutaneous anaplastic large cell lymphoma Br J Dermatol Whittaker et al, 2016. How I treat mycosis fungoides and Sézary syndrome Blood Wilcox et al, 2016. Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management Am J Hematol. Zinzani et al, 2016. Panoptic clinical review of the current and future treatment of relapsed/refractory T-cell lymphomas: Cutaneous T-cell lymphomas Crit Rev Oncol Hematol. Sicard et al, 2014. IPH4102, a Humanized KIR3DL2 Antibody with Potent Activity against CutaneousT-cell Lymphoma Cancer Research Kempf et al, 2011. EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma Blood Bouaziz et al, 2010. Absolute CD3+ CD158k+ lymphocyte count is reliable and more sensitive than cytomorphology to evaluate blood tumour burden in Sezary syndrome Br J Dermatol Willemze et al, 2010. Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up Ann Oncol. Agar et al, 2010. Survival outcomes and prognostic factors in mycosis fungoides/Sézary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal J Clin Oncol. Kim et al, 2003. Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrome: clinical prognostic factors and risk for disease progression Arch Dermatol. Bagot et al, 2001. CD4(+) cutaneous T-cell lymphoma cells express the p140-killer cell immunoglobulin-like receptor Blood Willemze et al, 1997. EORTC classiﬁcation for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer (EORTC) Blood