Lacutamab Earns FDA Breakthrough Therapy Designation for Sézary Syndrome Treatment

The FDA has granted Breakthrough Therapy designation (BTD) to the anti-KIR3DL2 cytotoxicity-inducing antibody, lacutamab, for the treatment of adult patients who developed relapsed or refractory Sézary syndrome after at least two prior systemic therapies including mogamulizumab.¹

Granting of a BTD is based on promising results from the phase II TELLOMAK study (NCT03902184) in which lacutamab demonstrated clinical activity in pretreated patients with Sézary syndrome and other mycosis fungoides. The efficacy was irrespective of KIR2DL2 expression, and the safety profile of lacutamab was tolerable.¹

A total of 107 patients with mycosis fungoides and a median age of 62 years were enrolled in the study. Patients had a median of four (range, 1–14) prior lines of systemic therapy. Patients were evaluated for the primary endpoint of objective response rate (ORR) by global response score and were analyzed in four categories: skin, blood, lymph nodes, and viscera.²

At a median follow-up of 11.8 months, lacutamab, 750 mg, achieved an ORR of 22.4% (95% CI, 15.6%-31.2%) in the overall study population, according to the revised International Consensus criteria. The ORR in skin was 29.0% (95% CI, 21.2%-38.2%), and the ORR in blood was 40.0% (95% CI, 24.6%-57.7%). The median time to response was one month, and the median progression-free survival (PFS) in the overall population was 10.2 months (95% CI, 6.5-16.8).²

In the subgroup of 48 patients with KIR3DL2 expression of 1% or greater, the ORR was 29.2% (95% CI, 18.2%-43.25) overall. Responses in skin and blood were 33.3% (95% CI, 21.7-47.5) and 41.2% (95% CI, 21.6-64.0), respectively. The subgroup also showed a median time to response of one month. The median PFS among patients with KIR3DL2 expression of 1% or greater was 12.0 months (95% CI, 5.6-20.0).²

Safety findings showed that serious treatment-related, treatment-emergent adverse events (TR TRAEs) occurred in 3.7% of patents. TR TREAs led to discontinuation of treatment in 2.8% of patients. The most common TR TRAEs observed were fatigue (11.2%), nausea (11.2%), asthenia (10.3%), and arthralgia (10.3%).²

The findings of the TELLOMAK study overall support further development of lacutamab to improve treatment of patients with cutaneous T-cell lymphoma, according to Pierluigi Porcu, MD, and colleagues.² With a BTD from the FDA, the development and regulatory review of the drug will be accelerated.

“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, in a press release. “The Breakthrough Therapy Designation underscores lacutamab’s potential to transform the patient’s care by achieving clinically meaningful efficacy and favorable safety profile compared to available therapies. This is an important step in Innate’s strategy for lacutamab. We are excited to work with the U.S. FDA to accelerate the development of this therapy.”¹

References

1. Innate Pharma announces U.S. FDA granted breakthrough therapy designation to lacutamab for relapsed or refractory Sézary syndrome. Business Wire. News release. February 17, 2025. Accessed February 18, 2025. https://bit.ly/3CVHKnY
2. Procu P, Bagot M, Ram-Wolff C, et al. Lacutamab in patients with relapsed and/or refractory mycosis fungoides: results from the TELLOMAK phase 2 trial. J Clin Oncol. 2024;42(16):7082. doi:10.1200/JCO.2024.42.16_suppl.7082