Authors
Matthew S. Davids, MD, MMSc, Alen Ostojic, MD, Susana Wargo, MD, Moana Hodari, MS, Jiefen Munley, MD, Richard Hermann, MD.
Introduction
AZD0486 is an IgG4 fully human CD19xCD3 bispecific T-cell engager that binds CD3 with low affinity to potentially reduce cytokine release upon T-cell activation while preserving effective T-cell cytotoxicity against malignant B cells. In a first-in-human phase 1 trial (NCT04594642), AZD0486 was active and well tolerated in patients with relapsed/refractory (R/R) follicular lymphoma or R/R diffuse large B-cell lymphoma (Gaballa S, et al. Blood. 2024;144:868; Hou JZ, et al. Blood. 2024;144:341). This study assesses fixed-duration subcutaneous (SC) AZD0486 as monotherapy or in combination with acalabrutinib in patients with R/R chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). This study is the first to evaluate AZD0486 in CLL/SLL and the first to evaluate SC AZD0486.
Methods
SOUNDTRACK-E (NCT06564038) is a phase 1/2 dose-escalation, global, multicenter trial of AZD0486 with 3 substudies, 1 of which is evaluating patients with R/R CLL/SLL. The study is recruiting patients aged ≥18 years with Eastern Cooperative Oncology Group performance status 0–2 and a histologically confirmed diagnosis. Patients with clinically significant central nervous system events (eg, seizure, stroke) or cardiovascular disease are excluded. The CLL/SLL substudy evaluates SC AZD0486 in patients with R/R CLL/SLL and includes a monotherapy cohort, in which patients with ≥2 prior lines of therapy (including Bruton tyrosine kinase inhibitor and BCL-2 inhibitor exposure) are eligible, and a combination therapy cohort that receives SC AZD0486 and acalabrutinib, in which patients with ≥1 prior line of therapy are eligible. In each cohort, SC AZD0486 is administered via a double step-up dosing schedule in cycle 1; the target dose is given every 2 weeks. Patients in the combination therapy cohort receive acalabrutinib 100 mg orally twice daily beginning at cycle 2. Dose escalation decisions will be based on a modified probability interval (mTPI-2) design. Approximately 46 patients for each cohort will be recruited. Primary objectives are to assess safety and tolerability, and to determine the recommended phase 2 dose for AZD0486 as monotherapy and in combination with acalabrutinib in patients with R/R CLL/SLL. Secondary objectives include efficacy endpoints, pharmacokinetics, and immunogenicity.
Results
Enrollment opened in October 2024 and is ongoing.
Conclusion
SOUNDTRACK-E will evaluate the safety and efficacy of AZD0486 as monotherapy or in combination with acalabrutinib for patients with CLL/SLL. This study is the first to evaluate SC AZD0486, and the first to evaluate AZD0486 in CLL/SLL.
Keywords : CLL/SLL; bispecific antibodies; relapsed/refractory
Please indicate how this research was funded.: Study funded by AstraZeneca.
Please indicate the name of the funding organization. : AstraZeneca