Abstract
Background: Rituximab in combination with chemotherapy (R [rituximab]-CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone]) is the standard first-line therapy for patients (pts) with DLBCL. With an aging population, unfit or frail pts who may not tolerate R-CHOP represent an increasing unmet need. There is also significant heterogeneity in how fitness for therapy is assessed. The simplified geriatric assessment (sGA) identifies three distinct categories (fit, unfit, and frail) based on age, activities of daily living (ADL), instrumental activities of daily living (IADL), and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G; Merli et al. J Clin Oncol 2021). Loncastuximab tesirine (loncastuximab tesirine-lpyl; Lonca), an antibody-drug conjugate comprising a humanized anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer toxin, is approved in relapsed or refractory (R/R) DLBCL based on data from the phase 2 LOTIS-2 pivotal trial (Caimi et al. Lancet Oncol 2021). The safety and efficacy of Lonca-R in combination is also being studied in pts with R/R DLBCL versus immunochemotherapy in an ongoing, separate study (LOTIS-5; NCT04384484). Aims: To determine the safety and efficacy of Lonca-R in previously untreated unfit/frail pts, as characterized by the sGA, in the LOTIS-9 clinical trial (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) pts with DLBCL. 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 pts, with fitness (Cohort A) and frailty (Cohort B) assessed using the sGA. Primary objectives are to assess efficacy (Cohorts A and B) and tolerability (Cohort B) of Lonca-R. The primary endpoint will be the complete response (CR) rate (Cohorts A and B) and tolerability defined by the percentage of patients completing a total of 4 cycles of therapy (Cohort B). Lonca-R treatment consists of R intravenously [IV] 375 mg/m2 on day 1 of cycles 1-4 (subcutaneously allowed starting at C2), Lonca 150 µg/kg IV on day 2 of cycle 1 and day 1 of cycle 2, and Lonca 75 µg/kg IV on day 1 of cycles 3 and 4. After completion of three Lonca-R cycles, pts who achieve CR or partial response (PR) will continue to receive 1 or 3 additional cycles of Lonca-R, respectively. Pts in Cohort A who do not achieve a CR or PR will discontinue treatment on study. Pts in Cohort B who achieve stable disease and derive clinical benefit, per the treating physician, may continue to receive an additional 3 cycles of Lonca-R. All pts will be followed every 12 weeks for 1 year, then every 24 weeks for up to 3 years, and then annually up to 5 years. Results: The study will open for recruitment in 2022. Summary/Conclusion: N/A
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