A novel CD19xCD3 bispecific T-cell engager, AZD0486, has demonstrated exceptional efficacy in treating relapsed/refractory follicular lymphoma, according to data presented at the recent American Society of Hematology (ASH) annual meeting. The phase I trial results reveal a striking 85% complete response rate, marking a significant advancement in non-chemotherapy treatment options for this challenging patient population.
Promising Efficacy in High-Risk Population
The trial enrolled heavily pretreated patients with high-risk disease characteristics, including some who had previously received CD19 CAR T-cell therapy. Dr. Yazeed Sawalha from Ohio State University Wexner Medical Center noted that the drug showed remarkable activity across various high-risk subgroups, including patients with POD24 (disease progression within 24 months of frontline chemoimmunotherapy).
"The drug is active. It showed very high response rate and the CR rate of 85%, including in subsets with high-risk disease," stated Dr. Sawalha. Notably, among patients achieving complete response, only two out of 41 experienced disease relapse during the follow-up period.
Innovative Design and Safety Profile
AZD0486 employs a unique design featuring low-affinity binding to CD3 T-cells, potentially reducing the risk of cytokine release syndrome (CRS). The treatment protocol involves intravenous administration with a two-step dosing schema, followed by bi-weekly dosing for up to two years.
The safety profile has proven encouraging, with most CRS cases being grade 1 and very few reaching grade 2. Dr. Sawalha emphasized that the risk of immune effector cell-associated neurotoxicity syndrome (ICANS) was notably low in follicular lymphoma patients treated with the double step-up dosing approach.
Future Development and Treatment Landscape
Plans are underway for a phase II trial to confirm these impressive complete response rates and assess response durability. Dr. David Bond highlighted the significance of having different therapeutic targets, noting that CD20 loss is a known resistance mechanism with currently approved bispecific antibodies.
"Having drugs that have a different target on the cell surface is attractive," Dr. Bond explained. "The numbers were small, but there were responses with patients that had prior T-cell engagers, with 75% of those patients responding."
Implications for Treatment Sequencing
The development of AZD0486 adds to the growing arsenal of non-chemotherapy options for follicular lymphoma treatment. Discussions are already underway regarding potential expansion into frontline therapy, although careful consideration of sequencing with existing CD20 T-cell engagers will be necessary.
Dr. Sawalha expressed optimism about the future landscape: "What's important is we're seeing these very active drugs hopefully or potentially replacing chemotherapy." This sentiment reflects a broader shift in the field toward more targeted, less toxic treatment approaches for follicular lymphoma patients.
