Xencor presents data from Phase 1 study of plamotamab

Xencor announced additional clinical data from expansion cohorts in its Phase 1 study of plamotamab, a CD20 x CD3 bispecific antibody, in patients with relapsed or refractory non-Hodgkin lymphomas. Data will be presented by Krish Patel, M.D., Director of the Lymphoma Program at Swedish Cancer Institute, in a poster session today from 6:00 p.m. to 8:00 p.m. CST at the 64th American Society of Hematology Annual Meeting in New Orleans, Louisiana. At data cut off on August 24, 2022, 44 patients with relapsed or refractory non-Hodgkin lymphoma had been enrolled before June 30, 2022 and received the recommended dose. Patients had a median age of 69 years and had received a median of 4 prior therapies. At baseline, 86% had advanced stage III or IV disease. Additionally, 50% of patients received CAR-T as a prior therapy. The primary disease at enrollment for these patients was diffuse large B-cell lymphoma, high-grade B-cell lymphoma, follicular lymphoma, and other lymphoma. The safety profile of plamotamab was consistent with previous results. The most common Grade 3 or 4 treatment-emergent adverse events across all patients were neutropenia, anemia and lymphopenia. Grade 3 immune effector cell-associated neurotoxicity syndrome was observed in one patient. AEs leading to plamotamab discontinuation occurred in nine patients, including four patients who discontinued due to COVID-19. Cytokine release syndrome, the most common AE, was observed in 70.5% of patients, and no patients experienced Grade 3 or 4 CRS. The efficacy analysis included both evaluable and intent-to-treat patient populations. Responses were assessed based on the Lugano Classification. In the efficacy evaluable population of patients with DLBCL or HGBCL, the overall response rate was 52.0%, and the complete response rate was 24.0%. For patients who received prior CAR-T therapy, the ORR was 50.0%, and the CR rate was 25.0%. In the ITT population, the ORR was 43.8%, and the complete response rate was 18.8%. The median duration of response for both populations was 126 days. In the efficacy evaluable population of patients with FL, the ORR was 87.5%, and the CR rate was 50.0%. In the ITT population, the ORR was 80.0%, and the CR rate was 40.0% . The mDOR for both populations had not been reached. An analysis of the plamotamab exposure-response relationship from the dose-escalation portion of the Phase 1 study examined IL-6 levels, CRS incidence, high-grade AEs and overall response. First-dose CRS was related to maximum plamotamab concentration. The probability of CRS with step-up dosing, however, was better modeled using the magnitude of the step-up increment, as measured by the ratio of Cmax after dosing to the concentration prior to that dosing. Once the target dose was reached, there was no relationship of exposure to high-grade CRS. This analysis indicates the potential for a wide therapeutic window at the target dose and provides guidance for improving dosing regimens in future clinical studies of plamotamab.