Lacutamab in patients with relapsed and/or refractory mycosis fungoides: Long-term follow-up and translational data from the TELLOMAK phase 2 trial.

Abstract

2523 Background: The most common type of cutaneous T-cell lymphoma is Mycosis Fungoides (MF) accounting for 50-60% of cases. Extracutaneous involvement occurs mainly in lymph nodes or blood; 25% of patients are diagnosed at advanced stage with a 5-year survival of 15-25%. Lacutamab is a first-in-class monoclonal antibody designed to specifically deplete KIR3DL2-expressing cells via antibody-dependent cell-cytotoxicity and phagocytosis. KIR3DL2 is a killer immunoglobulin-like receptor expressed in MF patients. Methods: TELLOMAK is an international, multi-cohort phase 2 trial (NCT03902184). MF patients who had received at least 2 prior systemic therapies were treated with lacutamab 750 mg until disease progression or unacceptable toxicity. Primary endpoint was Objective Response Rate (ORR) by global response score based on the evaluation of 4 compartments: skin, blood, lymph nodes and viscera according to the International Consensus criteria Olsen 2011. Key secondary endpoints included duration of response (DoR), progression free survival (PFS), safety, and quality of life. Here we report long term follow-up data of MF patients. Results: As of October 17, 2024, recruitment was completed, with 107 MF patients enrolled. The median age was 62 years. The median number of previous systemic lines was 4 (range: 1-14). Median follow-up was 22.1 months (m) (95% CI 19.4, 23.6). Global confirmed ORR was 19.6% (CI 13.2, 28.1; Olsen 2011), and response in skin was 29.0% (CI 21.2, 38.2). Median time to response was 2.8 m (min, max 1-37) and median DoR was 13.8 m (7.4, NE), median PFS was 10.2 m (CI 8.0, 15.4). Among the KIR3DL2 ≥1% pts (N = 48), ORR was 20.8% (CI 11.7, 34.3; Olsen 2011), and response in skin was 33.3% (CI 21.7, 47.5), median DoR was 13.8 m (CI 4.6, NE) and median PFS 11.8 m (CI 5.6, 16.8). Among the KIR3DL2 < 1% pts (N = 59), ORR was 18.6% (CI 10.7;30.4; Olsen 2011), and response in skin was 25.4 (CI 16.1, 37.8), median DoR was 15.7 m (CI 5.1, NE) and median PFS 9.5 m (CI 6.5;16.6). Grade ≥ 3 related Treatment-Emergent Adverse events (TEAEs) were observed in 5/107 (4.7%) patients, serious related TEAEs in 4/107 (3.7%) patients and related TEAEs leading to study drug discontinuation in 3/107 (2.8%) patients. The most common ( > 10%) related TEAEs were fatigue (12.1%), nausea (13.1%), asthenia (11.2%) and arthralgia (11.2%). Data from additional key endpoints and translational data will also be presented. Conclusions: The long-term follow-up data from the heavily pre-treated MF population enrolled to the TELLOMAK study confirms promising clinical activity of lacutamab regardless of KIR3DL2 expression, with ORR 20.8%, a median duration of response of 13.8 m, a median PFS of 10.2 m and a favorable safety and tolerability profile. These data support the further development of lacutamab in an effort to bring improved treatments to patients with MF. Clinical trial information: NCT03902184 // EU CT number: 2023-507777-18-00 .