Lacutamab (IPH4102) is a first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody, which is currently in clinical trials 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 90% of patients with certain aggressive CTCL subtypes, in particular, Sézary syndrome. It is expressed by up to 50% of patients with peripheral T-cell lymphoma (PTCL). It has a restricted expression on normal tissues.
Mechanism of action
Lacutamab is being investigated in mycosis fungoides, Sézary syndrome as well as in peripheral T-cell lymphoma.
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 endpoints are progression-free survival, duration of response, quality of life and adverse events.
About Lacutamab in peripheral T-cell lymphoma
Two clinical trials will investigate lacutamab in KIR3DL2-expressing peripheral T-cell lymphoma (PTCL) patients who have received at least one prior systemic therapy. Lacutamab is being evaluated:
- In a multi-center, Phase 1b clinical trial as a single agent in approximately 20 relapsed patients expressing KIR3DL2. The trial is designed to evaluate safety, as well as characterize clinical outcomes, pharmacokinetics and immunogenicity of lacutamab alone in PTCL. Further expansion will be determined based on preliminary efficacy signals.
- In a multi-center, randomized Phase 2 trial in combination with GEMOX in relapsed/refractory patients expressing KIR3DL2. This study will include approximately 60 patients. The combination trial, KILT (anti-KIR in T-Cell Lymphoma), is being conducted by the Lymphoma Study Association (LYSA) and its operational organization Lymphoma Academic Research Organisation (LYSARC); it will evaluate the efficacy and safety of lacutamab in combination with chemotherapy GEMOX in prescreened patients, with progression-free survival as the primary endpoint.
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