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, and peripheral T cell lymphoma (PTCL). 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

Mechanism of action lacutamab

 

 

Lacutamab is being investigated in mycosis fungoidesSézary 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. 
  • Granted orphan drug status in the European Union and in the United States for the treatment of CTCL.


About TELLOMAK

TELLOMAK (NCT03902184) is a global, open-label, multi-cohort Phase 2 clinical trial recruiting patients with Sézary syndrome and mycosis fungoides (MF) in the United States and Europe. Specifically:  

  • Cohort 1: lacutamab being evaluated as a single agent in approximately 60 patients with Sézary syndrome who have received at least two prior systemic therapies, including mogamulizumab. The Sézary syndrome cohort of the study could enable the registration of lacutamab in this indication. 
  • Cohort 2: lacutamab being evaluated as a single agent in patients with MF that express KIR3DL2, as determined at baseline with a Simon 2-stage design. 
  • Cohort 3: lacutamab being evaluated as a single agent in patients with MF that do not express KIR3DL2, as determined at baseline, with a Simon-2 stage design.
  • All comers: lacutamab being evaluated as a single agent in patients with both KIR3DL2 expressing and non-expressing MF to explore the correlation between the level of KIR3DL2 expression and treatment outcomes utilizing a formalin-fixed paraffin embedded (FFPE) assay under development as a companion diagnostic.

The trial is now fully enrolled. The primary endpoint of the trial is objective global response rate. Key secondary endpoints are progression-free survival, duration of response, overall survival, quality of life, pharmacokinetics and immunogenicity and adverse events. 

Positive results from TELLOMAK Phase 2 study with lacutamab in patients with Sézary syndrome were presented at ASH annual meeting 2023.  

About Lacutamab in peripheral T-cell lymphoma

A Phase 2 KILT (anti-KIR in T Cell Lymphoma) trial, led by the Lymphoma Study Association (LYSA) is an ongoing investigator-sponsored, randomized trial to evaluate lacutamab in combination with chemotherapy GEMOX (gemcitabine in combination with oxaliplatin) versus GEMOX alone in patients with KIR3DL2-expressing relapsed/refractory peripheral T-cell lymphoma. 

Publications, posters and presentations