ABCL-339: Clinical Activity of Loncastuximab Tesirine (Lonca) Plus Ibrutinib in Non-Hodgkin Lymphoma: Updated LOTIS-3 Phase 1 Results

Abstract

<h3>Context</h3> The treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) remains an area of unmet need. Combination therapies may improve treatment outcomes. <h3>Objectives</h3> Primary objective of a Phase 1/2 study (NCT03684694; Phase 1 part): Characterize the safety and tolerability of Lonca (an antibody-drug conjugate comprising a humanized anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer toxin) plus ibrutinib (a Bruton's tyrosine kinase inhibitor) and identify the maximum tolerated dose (MTD) or the recommended Phase 2 dose and schedule. Secondary objective: Evaluate antitumor effects. <h3>Design</h3> Dose escalation and dose expansion, open-label, single-arm, combination study in patients (≥18 years) with R/R DLBCL or R/R MCL. <h3>Interventions</h3> MTD was determined during dose escalation as Lonca 60 µg/kg IV every 3 weeks (Q3W) for 2 cycles and oral ibrutinib 560 mg/day PO for up to 1 year. After disease assessment at Week 14, patients with partial response/stable disease may receive 2 additional Lonca cycles Q4W at Cycles 5–6. <h3>Results</h3> At data cut-off (January 4, 2021), 30 patients with DLBCL (non-germinal center B-cell [non-GCB] DLBCL 24; GCB DLBCL 6) and 7 with MCL received the MTD during Phase 1. Median patient age: 72 years (range 40–91); 28 (75.7%) had Stage 4 disease. Patients received a median of 2 (range 1–6) prior therapies. Patients received a median of 2 Lonca cycles (range 1–4) and 4 (range 1–14) ibrutinib cycles. Median treatment duration: 105 days (range 18–379). Treatment-emergent adverse events (TEAEs) occurred in 37/37 (100%) patients. Grade ≥3 TEAEs occurred in 24/37 (64.9%) patients; the most common (≥5%) were anemia (4 [10.8%]), neutropenia (4 [10.8%]), thrombocytopenia (2 [5.4%]), and fatigue (2 [5.4%]). TEAEs leading to treatment discontinuation occurred in 3 (8.1%) patients. Overall response rate (ORR; 36 evaluable patients) was 63.9% (complete response 36.1%; partial response 27.8%). ORR for non-GCB DLBCL, GCB DLBCL, all DLBCL, and MCL patients was 66.7%, 20.0%, 58.6%, and 85.7%, respectively. <h3>Conclusions</h3> Results indicate that Lonca 60 µg/kg plus ibrutinib 560 mg has encouraging antitumor activity with manageable toxicity in R/R DLBCL and R/R MCL. <h3>Research Funding</h3> ADC Therapeutics SA