Surovatamig (AZD0486) is a novel CD19 × CD3 bispecific T-cell engager (TCE) designed to redirect T cells against CD19-expressing B-cell malignancies. The therapy is being developed by AstraZeneca, which acquired global rights to the asset through its USD 1.27 billion acquisition of Teneobio in 2021. Surovatamig is being investigated across a broad range of B-cell malignancies, including follicular lymphoma, DLBCL, and B-cell acute lymphoblastic leukemia (B-ALL), to achieve deep, durable responses while maintaining a manageable safety profile. As the treatment landscape increasingly shifts toward bispecific antibodies and other T-cell–redirecting therapies, surovatamig has emerged as a promising next-generation immunotherapy candidate.

Building on this development program, AstraZeneca is evaluating surovatamig in previously untreated follicular lymphoma in combination with rituximab in the Phase III SOUNDTRACK-F1 trial. Initial data from the trial, evaluating surovatamig in combination with rituximab in patients with previously untreated follicular lymphoma. The combination demonstrated a high overall response rate, deep complete responses, and encouraging minimal residual disease negativity, while maintaining a manageable safety profile characterized primarily by low-grade cytokine release syndrome and limited neurotoxicity. 

Key Efficacy Highlights:

• 43 patients enrolled: DL1 (2.4 mg surovatamig plus 375mg/m2 rituximab, N=22) and DL2 (7.2 mg surovatamig plus 375mg/m2 rituximab, N=21); Median follow-up: 6.3 months

• Best Overall Response Rate (ORR): 95% and  100% (DL1 and DL2)

• Complete Response (CR) Rate: 84% and 85% 

• Minimal Residual Disease (MRD)-Negative Rate (evaluable patients): 75% vs. 100%

Key Safety Highlights: 

• Any-grade TEAEs: Reported in 100% of patients across both dose levels

• Most common TEAEs: (DL1 and DL2)

• Infusion-related reactions: 36% and 52% (predominantly rituximab-related)

• Fatigue: 36% and 43%

• Myalgia: 36% and 38% 

• Decreased neutrophil count: 36% and 38% 

• Grade ≥3 TEAEs: 41% and 43%

• Serious TEAEs: 18% and 29% 

• Cytokine Release Syndrome (CRS): 36% and 38%; mostly during step-up doses and after the initial target dose (all Gr 1–2)

• Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): One event in each arm, occurring during step-up dosing

• Surovatamig-related infusion reactions: One Grade 2 event in each arm

• No Grade 5 TEAEs, no treatment discontinuations due to TEAEs, and no new safety signals identified

KOL insights -

“Surovatamig’s low-affinity CD3 design may reduce cytokine release and neurotoxicity while maintaining potent antitumor activity. High complete response rates alongside low rates of severe immune-mediated toxicities could improve the feasibility of bispecific therapy in earlier-line follicular lymphoma.” – Expert Opinion

Conclusion -

Follicular lymphoma is the second most common subtype of non-Hodgkin lymphoma, with an estimated 17,212 cases in the United States in 2025. While the disease is generally slow-growing, advanced follicular lymphoma carries a significant risk of progression and transformation to aggressive lymphoma. The treatment landscape has evolved considerably with the approval of therapies including obinutuzumab (GAZYVA), tazemetostat (TAZVERIK), epcoritamab (EPKINLY/TEPKINLY), mosunetuzumab (LUNSUMIO), axicabtagene ciloleucel (YESCARTA), lisocabtagene maraleucel (BREYANZI), tisagenlecleucel (KYMRIAH), zanubrutinib (BRUKINSA), odronextamab (ORDSPONO), rituximab hyaluronidase (RITUXAN HYCELA), and others. Despite the success of CD20-directed antibodies such as rituximab and obinutuzumab in combination with chemotherapy, more than 25% of patients experience disease progression within three years, and chemotherapy-associated toxicities remain a concern, particularly in older patients. Against this backdrop, the Phase III SOUNDTRACK-F1 trial demonstrated that surovatamig plus rituximab achieved high ORR and CR rate, deep MRD negativity, and a manageable safety profile characterized primarily by low-grade CRS and limited neurotoxicity. Collectively, the results highlight the potential of surovatamig plus rituximab to become an effective chemotherapy-free frontline treatment option for patients with previously untreated follicular lymphoma.