Lacutamab in Patients with Advanced Sezary Syndrome: Results from an Interim Analysis of the Tellomak Phase 2 Trial

Abstract

Introduction: Cutaneous T-cell lymphoma (CTCL) is a rare form of non-Hodgkin lymphoma. Sezary syndrome (SS) is a rare and aggressive type of CTCL. It has a unique biology, with high expression of KIR3DL2 reported in more than 85% of patients (pts). SS is characterized by erythroderma, significant blood involvement with malignant SS cells, and lymphadenopathy. These pts suffer from debilitating itching and recurrent skin infections, often affecting quality of life (QoL). SS is distinguished by its poor prognosis, as the median survival of pts is approximately 5 years. 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. Methods TELLOMAK is an international, open-label, phase 2 trial with multiple cohorts (NCT03902184). 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. Pts should have blood stage B2 at screening based on central evaluation by flow cytometry. Pts with evidence of large cell transformation are excluded. lacutamab 750 mg is administered as an intravenous infusion weekly × 5 weeks (w), every 2 w × 10, then every 4 w until progression or unacceptable toxicity. Primary endpoint is Objective Response Rate (ORR) by global response score. Secondary endpoints include additional efficacy endpoints, safety, QoL and translational assessments. Results At the data cut-off of April 29, 2022, 38 pts were enrolled and 37 pts treated with a median follow-up of 10.9 months (m) (range: <1, 34 m). Median age was 69 years (range: 50, 86). At study entry, the median prior lines of systemic therapies was 6 (range: 2, 11), 94.6% (n=35) had stage IVA and 5.4% (n=2) had stage IVB. In the ITT population, Global Confirmed ORR was 21.6% (8/37; 95% CI 11.4, 37.2). Confirmed ORR in skin was 35.1% (13/37; 95% CI 21.8, 51.2). Confirmed ORR in blood was 37.8% (14/37; 95% CI 24.1, 53.9), with 21.6% (8/37) CR as best overall response. Furthermore, 1 of the 28 pts with lymph node involvement at baseline achieved a CR. Grade ≥ 3 Treatment-related (TR) Treatment-Emergent Adverse events (TEAEs) were observed in 6/37 (16.2%) pts, Serious TR TEAEs were observed in 2/37 (5.4%) and 4/37 (10.8%) pts discontinued study drug due to TEAE. Data from additional key endpoints will be presented. 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.