FDA Grants Breakthrough Designation to Innate Pharma’s Lacutamab for Sézary

Innate Pharma SA, a global, clinical-stage biotechnology company developing immunotherapies for cancer patients, announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to lacutamab, an anti-KIR3DL2 cytotoxicity-inducing antibody, for the treatment of adult patients with relapsed or refractory (r/r) Sézary syndrome (SS) after at least 2 prior systemic therapies including mogamulizumab.

The BTD is granted based on phase 1 study results as well as results from the phase 2 TELLOMAK study, where lacutamab demonstrated encouraging efficacy and a favourable safety profile in heavily pretreated, post-mogamulizumab patients with advanced Sézary syndrome.

“There is a high unmet medical need for patients with Sézary syndrome. In this aggressive and rare form of cutaneous T-cell lymphoma, patients in advanced disease often experience very poor quality of life and are in strong need of new, targeted treatment options,” commented Sonia Quaratino, MD, chief medical officer of Innate Pharma. “The Breakthrough Therapy Designation underscores lacutamab’s potential to transform the patient’s care by achieving clinically meaningful efficacy and favourable safety profile compared to available therapies. This is an important step in Innate’s strategy for lacutamab. We are excited to work with the US FDA to accelerate the development of this therapy.”

A Breakthrough Therapy Designation by the FDA is intended to accelerate the development and regulatory review in the US of drugs that are intended to treat a serious condition and that have shown encouraging early clinical results, which may demonstrate substantial improvement on a clinically significant endpoint over available medicines.

Lacutamab previously received a Fast Track designation by the FDA in 2019 for the treatment of adult patients with relapsed or refractory Sézary syndrome who have received at least two prior systemic therapies as well as a PRIME designation by European Medicines Agency in 2020.  

Innate continues to align with the regulatory agencies around the confirmatory phase 3 trial in CTCL and is actively seeking for a partner.

Cutaneous T-Cell Lymphoma (CTCL) is a heterogeneous group of non-Hodgkin’s lymphomas which arise primarily in the skin and are characterized by the presence of malignant clonal mature T-cells. CTCL accounts for approximately 4% of all non-Hodgkin’s lymphomas and has a median age at diagnosis of 55-65 years. Mycosis fungoides, and Sézary syndrome, its leukemic variant, are the most common CTCL subtypes. The overall 5-year survival rate, which depends in part on disease subtype, is approximately 10% for Sézary syndrome. There are approximately 6,000 new CTCL cases in Europe and the United States per year.

Sézary syndrome is the leukemic variant of CTCL. Patients often experience very poor quality of life with severe and debilitating pruritus (chronic itchy skin). Despite recent advancements, Sézary syndrome is associated with a high relapse rate with currently available therapies.

Lacutamab is a first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody that 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 have 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 90% of patients with certain aggressive CTCL subtypes, in particular Sézary syndrome. It is expressed by up to 50% of patients with mycosis fungoides and peripheral T-cell lymphoma (PTCL). It has a restricted expression on normal tissues.

Lacutamab is granted European Medicines Agency (EMA) PRIME designation and US Food and Drug Administration (FDA) granted Fast Track designation and Breakthrough Therapy Designation for the treatment of patients with relapsed or refractory Sézary syndrome who have received at least two prior systemic therapies. Lacutamab is granted orphan drug status in the European Union and in the United States for the treatment of CTCL.

TELLOMAK (NCT03902184) is a global, open-label, multi-cohort phase 2 clinical trial in 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 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.

Innate Pharma S.A. is a global, clinical-stage biotechnology company developing immunotherapies for cancer patients. Its innovative approach aims to harness the innate immune system through three therapeutic approaches: multi-specific NK Cell Engagers via its ANKET (Antibody-based NK cell Engager Therapeutics) proprietary platform and Antibody Drug Conjugates (ADC) and monoclonal antibodies (mAbs).

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