ICML 2025 | The safety and efficacy of surovatamig (AZD0486) in R/R DLBCL: findings from a Phase I trial

T cell engagers are off-the-shelf therapies that may overcome some of the limitations associated with CAR T-cell therapy. Several CD20 x CD3 T-cell engagers are currently being developed to treat B-cell lymphomas and the T-cell engagers show clinically meaningful efficacy. However, therapeutic options remain limited for patients who relapse after or are refractory to CD20xCD3 T-cell engagers, and loss of CD20 expression represents a significant clinical challenge to CD20xCD3 T-cell engagers’ use. In addition, treatment options are limited for patients who relapse or are refractory after CAR T-cell therapy, as well as for those who are ineligible for CAR T-cell therapy. 

Surovatamig, formerly known as AZD0486, is a novel IgG4 fully human CD20xCD3 bispecific T-cell engager with attenuated CD3 binding to minimize cytokine release. We presented safety and efficacy data from the Phase I first-in-human ongoing dose escalation of surovatamig in patients with refractory/relapsed DLBCL. In total, patients received a fixed duration of surovatamig intravenously for two years. 

As for safety data, in 77 patients who received surovatamig in double-step-up dosing, any-grade CRS and ICANS were observed in 49% and 20% of patients, respectively. As for CRS, all events were grade 1 or 2, and median time to first CRS and median time to resolution was one day each, and 27% of patients received tocilizumab. Grade 1/2 ICANS events were observed in 10 patients, and grade 3 ICANS occurred in 4 patients that were transient and reversible. Median time to first ICANS and median time to resolution was one day each and no seizures were observed. Overall, most of all adverse events were manageable and the safety profile of surovatamig was acceptable. 

As for baseline patient background, more than 70% of patients had a history of refractory to last line of therapy and more than 40% of patients received prior CAR-T therapy, CD19 CAR-T therapy, and 13% of patients received prior CD20 T-cell engagers. So that is to say, most of enrolled patients had high-risk features and heavily pre-treated disease. However, surovatamig at target doses 7.2 mg or higher showed promising efficacy, such as overall response rate 74% and CR rate 63% at the target dose of 25 mg, including the CD20 CAR-T exposed patients. The median duration of response and the median duration of CR were not reached, and the 12 months estimated DOR was 77% and duration of CR was 87%. Even though the limited follow-up duration with a small number of patients at this point, there seemed to be a potential plateau in duration of response and duration of CR. So, surovatamig has demonstrated high efficacy and a manageable safety profile in relapsed/refractory DLBCL patients. As a novel CD20 targeting T-cell engager, surovatamig is expected to play an important role in DLBCL treatment in the near future.

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