ABCL-272 A Phase 2, Open-Label Study of Loncastuximab Tesirine in Combination With Rituximab (Lonca-R) in Previously Untreated Unfit/Frail Patients With Diffuse Large B-Cell Lymphoma (LOTIS-9)

Background: Rituximab in combination with chemotherapy (R [rituximab]-CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone]) is standard first-line therapy for patients with diffuse large B-cell lymphoma (DLBCL). With an aging population, unfit or frail patients who may not tolerate R-CHOP represent an increasing unmet need. Aim: To determine the safety and efficacy of the approved loncastuximab tesirine (loncastuximab tesirine-lpyp; Lonca), an antibody-drug conjugate comprising a humanized anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer toxin, in combination with rituximab (Lonca-R) in previously untreated unfit/frail patients (LOTIS-9; NCT05144009). Methods: This is a phase 2, open-label, response-adapted study of Lonca-R in previously untreated unfit (Cohort A) or frail (Cohort B) patients with DLBCL. The simplified geriatric assessment (sGA), which identifies three categories of fitness (fit, unfit, and frail) based on age, activities of daily living (ADL), and instrumental activities of daily living (IADL), and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) will be utilized to differentiate the cohorts. Key inclusion criteria include diagnosis of DLBCL (including DLBCL transformed from indolent lymphoma), high-grade B-cell lymphoma, or grade 3b follicular lymphoma; Eastern Cooperative Oncology Group performance status of 0–2; and measurable disease (2014 Lugano Classification). Each cohort will enroll 40 patients, with fitness (Cohort A) and frailty (Cohort B) assessed using the sGA. Primary objectives: efficacy (Cohorts A and B) and tolerability (Cohort B) of Lonca-R. Primary endpoints: complete response (CR) rate (both Cohorts) and tolerability (Cohort B) following completion of 4 therapy cycles. Lonca-R treatment consists of R intravenously [IV] 375 mg/m² on day 1/cycles 1–4, (subcutaneously allowed starting at C2), Lonca 150 µg/kg IV on day 2/cycle 1 and day 1/cycle 2, and 75 µg/kg IV on day 1/cycles 3 and 4. Patients who achieve CR or partial response (PR) after three cycles will receive 1 or 3 additional cycles of Lonca-R, respectively. Cohort B patients who achieve stable disease may continue to receive 3 additional cycles. All patients will be followed for up to 5 years. Results: The study opened for recruitment in April 2022. This abstract was accepted for publication only at the 2022 EHA Congress. Funding: ADC Therapeutics SA; medical writing: CiTRUS Health Group.