SOUNDTRACK-B: A phase 2 single-arm study to evaluate the efficacy and safety of surovatamig (AZD0486) in relapsed or refractory B-cell non-Hodgkin lymphoma

Abstract

Abstract Background and Significance: Management of relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHL) is challenging. Surovatamig (formerly AZD0486), an IgG4 fully human CD19xCD3 bispecific T-cell engager, yielded high response rates with tolerable safety in patients with heavily pretreated follicular lymphoma (FL) and diffuse large B-cell lymphoma in a first-in-human phase 1 study (NCT04594642) (Hou JZ, et al. Blood. 2024;144:341; Yoon DH, et al. HemaSphere. 2025;9(S1):3398). SOUNDTRACK-B is a phase 2 study assessing the efficacy and safety of surovatamig in patients with R/R FL and R/R large B-cell lymphoma (LBCL). Study Design and Methods SOUNDTRACK-B (NCT06526793) is a modular, phase 2, global, multicenter, single-arm, open-label study of surovatamig monotherapy in patients with R/R FL and R/R LBCL. The study is currently recruiting patients aged ≥18 years with an Eastern Cooperative Oncology Group performance status of 0–2 who have received at least 2 prior lines of systemic therapy. Patients who received prior treatment with CAR T-cell therapy or other T-cell engagers are eligible. Exclusion criteria include history of transformation to an aggressive lymphoma for patients with R/R FL (eg, LBCL or high-grade B-cell lymphoma); active central nervous system (CNS) involvement by B-NHL; history or presence of clinically relevant CNS pathology (eg, epilepsy, seizure, stroke); or major cardiac abnormalities. SOUNDTRACK-B consists of 2 modules. Module 1 is enrolling patients with R/R FL, and module 2 will enroll patients with R/R LBCL. In both modules, surovatamig will be administered as an intravenous infusion with step-up dosing during cycle (C) 1. In both modules, the target dose will first be given on C1 day (D) 15, then every 2 weeks on D1 and D15 of the following cycles. Patients whose disease achieves complete response (CR) and who have received at least 6 cycles of treatment will receive surovatamig every 4 weeks on D1 of subsequent cycles. The recommended phase 2 dose for the target dose is 7.2 mg for module 1 (R/R FL). Each treatment cycle is 28 days. The treatment period will be up to 24 cycles for module 1 (R/R FL) and up to 12 cycles for module 2 (R/R LBCL), or until disease progression or unacceptable toxicity. Peripheral blood samples for minimal residual disease (MRD) assessment will be collected at baseline and throughout the study period at time points generally relevant to response assessment; samples for MRD assessment will be analyzed centrally. Approximately 120 patients will be enrolled in each module. The primary endpoint is overall response rate, defined as proportion of patients achieving either partial response or CR based on Lugano 2014 response criteria as determined by an independent review committee. Secondary endpoints include duration of response, CR rate, MRD-negative CR rate, and safety. Enrollment in module 1 (R/R FL) began in November 2024.