AstraZeneca's surovatamig, a next-generation CD19xCD3 bispecific T-cell engager (BiTE), demonstrated promising efficacy and safety results in treating patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) according to preliminary data from the Phase I/II SYRUS clinical trial presented at the 2025 Congress of the European Hematology Association (EHA 2025) in Milan, Italy.
Trial Design and Patient Population
The global, multicentre, open-label, single-arm SYRUS clinical trial (NCT06137118) enrolled 120 patients with R/R B-ALL across three arms: dose escalation, dose optimisation and expansion. The study evaluated the safety, tolerability, pharmacodynamics, pharmacokinetics and clinical activity of surovatamig as monotherapy in patients aged 12 and over.
In the dose-escalation arm, patients with CD19-positive Philadelphia chromosome-positive or negative (Ph+ or Ph-) B-ALL who had failed at least one or two previous therapies received intravenous surovatamig at escalating dose levels up to 15mg.
Efficacy Results Show Dose-Dependent Response
The trial demonstrated encouraging dose-dependent efficacy results. Complete remission or complete remission with incomplete recovery rates were 46% (6 of 13), 58% (7 of 12) and 83% (5 of 6) at dose levels 1, 2, and 3 respectively. Overall response rates reached 67% at dose level 1 and 100% at dose level 2.
Notably, patients previously exposed to CD19-targeted therapy also demonstrated promising efficacy, suggesting potential utility even in heavily pretreated populations.
Safety Profile Appears Manageable
The safety profile of surovatamig appeared manageable across dose levels. At dose level 1, cytokine release syndrome occurred in 31% (4 of 13) of patients during the step-up dosing phase and in 30% (3 of 10) during the target dose phase, with no grade 4 events observed in either case.
A low incidence of immune effector cell-associated neurotoxicity syndrome was reported during both the step-up dosing phase and the target dose phase. Two patients experienced dose-limiting toxicities but continued to receive the targeted dose. Importantly, no patients discontinued treatment due to surovatamig-related adverse events and no new safety signals were identified.
Addressing Unmet Medical Need in R/R B-ALL
B-ALL accounts for between 7% and 85% of total ALL cases and represents an aggressive hematologic malignancy characterized by the overproduction of immature lymphoid cells in the bone marrow, blood and other organs. According to GlobalData's epidemiology forecast, the number of diagnosed incident cases in eight major markets is projected to increase from 25,636 in 2025 to 26,482 by 2029 at an annual growth rate of 1.16%.
Despite advances with existing BiTEs such as Amgen's Blincyto (blinatumomab), antibody-drug conjugates such as Pfizer's Besponsa (inotuzumab ozogamicin) and chimeric antigen receptor T-cell (CAR-T) therapies such as Autolus Therapeutics' Aucatzyl (obecabtagene autoleucel), R/R B-ALL remains an area of high unmet need due to limited durability of response, CD19 relapse and lack of accessible curative options beyond stem cell transplant.
Next-Generation Design Features
Surovatamig is Fc-engineered for extended half-life and optimized CD3 binding, enabling intermittent dosing and controlled T-cell activation. This design offers a more convenient and potentially safer alternative to Blincyto's continuous infusion requirement.
The FDA approved Blincyto, the first bispecific T-cell engager, in 2014 for adults with Ph- R/R B-ALL, with its label expanded in 2017 to include Ph+ and pediatric cases.
Market Outlook and Competition
Beyond R/R B-ALL, surovatamig is currently in Phase III trials as monotherapy for diffuse large B-cell lymphoma and in combination with Biogen's Rituxan (rituximab) for untreated follicular lymphoma.
According to GlobalData's analyst consensus forecast, surovatamig's global sales are projected to reach $138 million by 2031, compared to $1.7 billion for Blincyto. However, Blincyto's loss of exclusivity in Europe (2025) and the US (2026) is expected to significantly reduce its future sales, potentially creating market opportunities for next-generation alternatives like surovatamig.
