Abstract A056: Bispecific T-cell engagers and antibody-drug conjugtes for the treatment of lymphomas

Abstract Two bispecific antibodies, glofitamab and epcoritamab, are CD20xCD3 targets approved to treat R/R DLBCL. Two antibody drug conjugates, brentuximab vedotin, with a CD30-directed monoclonal antibody, is approved for cHL and R/R DLBCL, and polatuzumab vedotin, with a CD79b directed monoclonal antibody, is approved for R/R DLBCL. Unique mechanisms of action for each agent, the path to FDA approval from preclinical stage, FIH trials and clinical trials for each agent, as well as comparisons of adverse events between the two classes of therapeutic agents are shown, as well as how these two distinct classes of agents developed mechanistically and clinically for lymphomas, hematologic cancers with generally poor prognosis. Glofitamab was evaluated and complete responses were ongoing at 12 months. The 12-month PFS was 37% (95% CI, 28 to 46). Discontinuation of glofitamab due to adverse events occurred in 9% of the patients. Glofitamab combined with tislelizumab in R/R DLBCL was also evaluated in a single-center pilot trial. In a study investigating epcoritamab, the ORR was 63.1% (95% CI, 55.0 to 70.6) and the CR rate was 38.9% (95% CI, 31.2 to 46.9). The median duration of response was 12.0 months (among complete responders: not reached). Overall and CR rates were similar across key prespecified subgroups. The most common TEAEs were CRS (49.7%); (grade 1 or 2: 47.1%; grade 3: 2.5%), pyrexia (23.6%), and fatigue (22.9%). ICANS occurred in 6.4% of patients with one fatal event. Epcoritamab also induced potent anti-tumor activity against malignant B-cells from patients with DLBCL, FL and MCL, irrespective of prior CD20 monoclonal antibody treatment. Brentuximab vedotin was shown to be effective in R/R DLBCL in the ECHELON-3 trial, a randomized, double-blind, placebo-controlled, multicenter, phase 3 study comparing BV + Len + R with placebo + Len + R. With a median follow-up of 16.4 months, the mOS was 13.8 months with BV + Len + R versus 8.5 months with placebo + Len + R (HR, 0.63 [95% CI, 0.45 to 0.89]). The mPFS was 4.2 months with BV + Len + R versus 2.6 months with placebo + Len + R (HR, 0.53 [95% CI, 0.38 to 0.73]). The ORR was 64% [95% CI, 55 to 73] with BV + Len + R and 42% (95% CI, 33 to 51) with placebo + Len + R; CR rates were 40% and 19%, respectively. TEAEs occurred in 97% of patients in both arms, including neutropenia, thrombocytopenia, diarrhea, and anemia. Polatuzumab vedotin was also evaluated in R/R DLBCL. Polatuzumab vedotin plus bendamustine and rituximab (pola + BR) received regulatory approvals for R/R DLBCL based on primary results from the randomized arms of the GO29365 study. Significant survival benefit with pola + BR vs BR persisted (mPFS 9.2 vs 3.7 months [HR, 0.39; 95% CI, 0.23-0.66]; mOS, ([12.4 vs 4.7 months [HR 0.42; 95% CI 0.24-0.72]). Pola + BR was shown to be an effective treatment option for patients with R/R DLBCL, with a well-characterized and manageable safety profile. Citation Format: Priya Hays. Bispecific T-cell engagers and antibody-drug conjugtes for the treatment of lymphomas [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr A056.