lacutamab (IPH4102)

This review emphasizes the necessity for ongoing research and individualized treatment plans while highlighting the promise of these cutting-edge techniques to enhance outcomes for patients with advanced CTCL.

P2, N=56, Recruiting, The Lymphoma Academic Research Organisation | Trial completion date: Jan 2027 --> Jan 2028 | Trial primary completion date: Jan 2025 --> Jan 2026

P2, N=170, Active, not recruiting, Innate Pharma | Trial completion date: Oct 2024 --> Jan 2026

P1, N=20, Completed, Innate Pharma | Active, not recruiting --> Completed | N=40 --> 20 | Trial completion date: Jul 2024 --> Feb 2024

Moreover, anti-PD1 (nivolumab), anti-PDL1 (pembrolizumab, atezolizumab), anti-CD52 (alemtuzumab), anti-KIR3DL2-CD158k (lacutamab), and anti-CD70 (cusatuzumab) have been tested or are under investigations in phase II trials. In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in mycosis fungoides, primary cutaneous anaplastic large T-cell lymphoma, lymphomatoid papulosis; anti-CCR4 (mogamulizumab) in Sezary syndrome; anti-CD123 (tagraxofusp) in blastic plasmocytoid cell neoplasm. The expression of these epitopes on neoplastic cells in skin biopsies or blood samples plays a central role in the management of PCTCL patients. This narrative review aims to provide readers with an update on the latest advances in the newest therapeutic options for PCTCLs.

To further develop novel-lacutamab combinations, the combinability of lacutamab with therapies used in R/R or frontline PTCL e.g., pralatrexate or CHOP, respectively, was tested. These data inform the future development of lacutamab to provide additional therapeutic options that may improve outcomes for PTCL patients, including those who relapse or are refractory to available therapies. A Phase 2 study evaluating the combination of lacutamab with GemOx is ongoing (NCT04984837) based on pre-clinical observations that GemOx improves lacutamab-induced ADCC by NK cells.

Conclusion In this SS cohort from the TELLOMAK study, our data confirm that lacutamab monotherapy shows promising clinical activity in a R/R population previously treated with 2 or more prior systemic therapies including mogamulizumab, and an overall favourable safety profile. Continued evaluation of this new targeted treatment option for patients with SS is warranted.

P1, N=40, Active, not recruiting, Innate Pharma | Recruiting --> Active, not recruiting

P2, N=170, Active, not recruiting, Innate Pharma | Recruiting --> Active, not recruiting | Trial completion date: Mar 2024 --> Oct 2024 | Trial primary completion date: Mar 2023 --> Oct 2023

P1, N=40, Recruiting, Innate Pharma | Trial completion date: Apr 2023 --> Jul 2024 | Trial primary completion date: Dec 2022 --> Nov 2023

To date vorinostat, is the only drug that has been approved by the FDA for the treatment of pts with CTCL with cutaneous manifestations who have received 2 prior systemic therapies...Cohort 1, for which preliminary data is reported here, is designed to evaluate safety and efficacy of single agent lacutamab in pts with relapsed/refractory SS after at least 2 prior systemic therapies including mogamulizumab...Conclusion In this highly refractory SS cohort from the TELLOMAK study, our preliminary data demonstrate that lacutamab shows clinical activity and favourable safety profile. Continued evaluation of this new targeted treatment option for patients with SS is warranted.

Secondary objectives are to assess the clinical activity and to characterize the pharmacokinetics, and immunogenicity of lacutamab. The trial is currently enrolling in 11 medical centers in the US and South Korea.