Lacutamab (IPH4102) is a first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody, designed for treatment of cutaneous T-cell lymphoma (CTCL), an orphan disease. This group of rare cutaneous lymphomas of T lymphocytes has a poor prognosis with few efficacious and safe 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 them patients with certain aggressive CTCL subtypes, in particular, Sézary syndrome. It has a restricted expression on normal tissues.
Mechanism of action
Lacutamab is being investigated in mycosis fungoides and Sézary syndrome.
European Medicines Agency (EMA) granted PRIME designation in November 2020 to lacutamab for the treatment of patients with relapsed or refractory Sézary syndrome who have received at least two prior systemic therapies.
The US Food and Drug Administration (FDA) granted Fast Track designation in January 2019.
Grantedorphan drug status in the European Union and in the United States for the treatment of CTCL.
TELLOMAK is a global, open-label, multi-cohort Phase 2 clinical trial recruiting patients with advanced T-cell lymphomas (TCL) in the United States and Europe. TELLOMAK is expected to recruit up to 150 patients, with lacutamab evaluated:
- As a single agent in approximately 60 patients with Sézary syndrome who have received at least two prior systemic therapies, including mogamulizumab
- As a single agent in approximately 90 patients with mycosis fungoides (MF) who have received at least two systemic therapies
In patients with MF, the study is designed to evaluate the benefit of lacutamab according to KIR3DL2 expression. The study comprises two cohorts in MF, testing lacutamab in KIR3DL2 expressing and non-expressing patients determined at baseline. These cohorts follow a Simon 2-stage design that will terminate early if treatment is considered futile. The Sézary syndrome cohort of the study could enable the registration of lacutamab in this indication.
The primary endpoint of the trial is objective response rate. Key secondary measures include incidence of treatment emergent adverse events, quality of life, overall response rate, progression-free survival and overall survival.
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