About this program
IPH4102 is a first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody, designed for treatment of T-cell lymphomas.
Cutaneous T-cell lymphomas (CTCL), an orphan disease, 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 (tMF). 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.The US Food and Drug Administration (FDA) has granted Fast Track designation to IPH4102 for the treatment of adult patients with relapsed or refractory Sézary syndrome who have received at least two prior systemic therapies.
TELLOMAK, a global, multi-cohort, Phase II study evaluating the potential of IPH4102 in different subtypes of T-cell lymphomas, will be initiated in the first half of 2019
Mechanism of action of anti-KIR3DL2
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).
- 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. Results of the dose-escalation were presented at the EORTC CLTF meeting in October 2017.
- The cohort expansion enrolled 15 patients with Sézary Syndrome and 4 tMF 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. Exploratory analyses are aimed at identifying biomarkers of clinical activity.
In a presentation at EORTC CLTF meeting in September 2018 and updated results presented at the 2018 ASH Annual Meeting, IPH4102 showed encouraging clinical activity, demonstrated by high response rate and long progression-free survival.
The Phase II study TELLOMAK evaluating the potential of IPH4102 in different subtypes of T-cell lymphomas will be initiated in the first half of 2019.
TELLOMAK is a global, open-label, multi-cohort Phase II study evaluating the efficacy and safety of IPH4102 in patients with different subtypes of T-cell lymphoma. TELLOMAK is planned to recruit up to 250 patients, with IPH4102 evaluated as a single agent in patients with Sezary syndrome and Mycosis Fungoides - MF (approximately 150 patients) and in combination with standard chemotherapy (gemcitabine and oxaliplatin) in patients with peripheral T-cell lymphoma - PTCL (approximately 100 patients). In patients with MF and PTCL, the study is designed to evaluate the benefit of IPH4102 according to KIR3DL2 expression.
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