Lacutamab in patients with relapsed and/or refractory mycosis fungoides: Results from the TELLOMAK phase 2 trial.

Abstract

7082 Background: Cutaneous T-cell lymphoma (CTCL) is a rare form of non-hodgkin’s lymphoma. The most common type of CTCL is Mycosis Fungoides (MF) accounting for 50-60% of cases, while Sezary Syndrome, the leukemic variant of MF accounts for 2-5% of cases. Extracutaneous involvement occurs mainly in lymph nodes or blood; 25% of patients (pts) are diagnosed at advanced stage with a 5-year survival of 15-25%. KIR3DL2 is a killer immunoglobulin-like receptor, expressed in 90% of SS pts, and 50% of MF pts. Lacutamab is a first-in-class monoclonal antibody designed to specifically deplete KIR3DL2-expressing cells via antibody-dependent cell-cytotoxicity and phagocytosis. Methods: TELLOMAK is an international, open-label, multi-cohort phase 2 trial (NCT03902184). MF pts who had received at least 2 prior systemic therapies were allocated to different cohorts according to KIR3DL2 expression in skin. Lacutamab 750 mg is administered as an intravenous infusion 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 International Consensus criteria (Olsen 2011; sensitivity analysis vs revised Olsen 2022). Secondary endpoints included other efficacy endpoints, safety, and quality of life. Here we report data of all MF patients, and according to KIR3DL2 status. Results: At the data cutoff of October 13, 2023, recruitment was completed, with 107 pts enrolled. Median age was 62 years. Median number of previous systemic lines was 4 (range: 1-14). Median follow-up was 11.8 months (m) (95% CI 9.9-13.8). ORR was 16.8% (CI 10.9, 25.0; Olsen 2011), and 22.4% (CI 15.6, 31.2; Olsen 2022), response in skin and blood was 29.0% (CI 21.2, 38.2) and 40.0% (CI 24.6, 57.7) respectively. Median time to response was 1.0 months and median PFS 10.2m (CI 6.5, 16.8). Among the KIR3DL2 ≥1% pts (N=48), ORR was 20.8% (CI 11.7,34.3; Olsen 2011), and 29.2% (CI 18.2, 43.2; Olsen 2022), response in skin and in blood was observed in 33.3% (CI 21.7, 47.5) and 41.2% (CI 21.6, 64.0) respectively. Median time to response was 1.0 month and median PFS was 12.0 m (CI 5.6, 20.0). Median duration of response was not reached. Grade ≥ 3 Treatment-related (TR) Treatment-Emergent Adverse events (TEAEs) were observed in 4/107 (3.7%) pts, serious TR TEAEs were observed in 4/107 (3.7%) pts and 3/107 (2.8%) pts discontinued study drug due to TR TEAEs. The most common (>10%) TR TEAEs were fatigue (11.2%), nausea (11.2%), asthenia (10.3%), and arthralgia (10.3%). Conclusions: The data from the heavily pre-treated MF population enrolled to the TELLOMAK study confirms promising clinical activity of lacutamab regardless of KIR3DL2 expression, with a favorable safety and tolerability profile. These data support the further development of lacutamab in an effort to bring improved treatments to patients with CTCL. Clinical trial information: NCT03902184 .