Lacutamab in patients with relapsed and refractory Sézary syndrome: Long term follow-up from the TELLOMAK phase 2 trial.

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2522 Background: Sézary syndrome (SS) is a rare and aggressive cutaneous T-cell lymphoma, which commonly expresses KIR3DL2, a killer immunoglobulin-like receptor, reported in ≥ 85% of patients. SS is characterized by erythroderma, significant blood involvement, lymphadenopathy and poor prognosis (10-20% 5-year survival). 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, Phase 2 trial with multiple cohorts (NCT03902184). We report here long term follow-up results from Cohort 1, evaluating lacutamab in patients with relapsed/refractory (R/R) SS after at least 2 prior systemic therapies including mogamulizumab. Lacutamab 750 mg is administered until progression or unacceptable toxicity. Primary endpoint was Objective Response Rate (ORR) based on the evaluation of 4 compartments: skin, blood, lymph nodes and viscera according to the International Consensus criteria Olsen 2011. Secondary endpoints included but were not limited to duration of response (DOR), progression free survival (PFS), safety, and quality of life assessments. Results: As of October 17, 2024, recruitment was completed with 63 SS patients enrolled. Median age was 69 years (range: 42-86), the median prior lines of systemic therapies were 5.0 (range: 2-13), 65.1% and 34.9 % patients had stage IVA1 and stage IVA2 at baseline respectively, all patients had blood involvement (B2), 63.5% had confluence of erythema covering ≥ 80% body surface area (T4), 34.9% had lymph node lymphoma involvement (N3). Median follow-up was 25.1 months (95% CI 21.0-29.4). Global confirmed ORR was 42.9% (CI 31.4-55.1) including 6 (9.5%) CRs who are all still in CR; with a median time to response of 2.8 months (range 1-10) and a median duration of response of 25.6 months (CI 11.0, NE). According to each compartment, ORR in skin was 52.4% (CI 40.3-64.2) including 9 (14.3%) CRs, ORR in blood was 50.8% (CI 38.8-62.7) including 21 (33.3) CRs, and ORR in lymph nodes was 28.8% (CI 18.3-42.3) including 9 (17.3) CRs. Median PFS was 8.3 months (CI 5.1-18.7). Grade ≥ 3 related Treatment-Emergent Adverse Events (TEAEs) were observed in 20.6% patients. Serious related TEAEs were observed in 9.5% patients and related TEAEs leading to study drug discontinuation in 6.3% patients. Data from additional key endpoints will be presented. Conclusions: The long term follow-up data from TELLOMAK study in a R/R SS population previously treated with 2 or more prior systemic therapies including mogamulizumab, confirm that lacutamab shows promising clinical activity with ORR 42.9% (95% CI 31.4-55.1) and median duration of response of 25.6 months (11.0, NE) and an overall favourable safety profile. These data support the further development of lacutamab in an effort to bring improved treatments to patients with SS. Clinical trial information: NCT03902184 // EU CT number: 2023-507777-18-00.

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