At the 2024 annual meeting of the American Society of Hematology (ASH), held on 7 December in San Diego, California, AstraZeneca presented interim results from a first-in-human trial of their novel bispecific T-cell engager (BiTE), AZD0486, in patients with relapsed or refractory follicular lymphoma (r/r FL).

The BiTE targets CD19 on the cancerous cells and CD3 on the surface of T-cells, recruiting the patient’s T-cells to attack the lymphoma and inducing cell lysis and T-cell proliferation. Patients in the trial had received at least two previous lines of therapy. There are already many approved therapies in this disease setting, including cell therapies, Johnson and Johnson’s Yescarta (axicabtagene ciloleucel), Norvartis’ Kymriah (tisagenlecleucel), and BMS’ Breyanzi (lisocabtagene maraleucel) - but these have had limited uptake due to a lack of qualified treatment centres and high cost. In 2022, Genetech’s Lunsumio (mosunetuzumab), a CD20xCD3 targeting BiTE, was approved for r/r FL patients after at least two prior lines of therapy, and in early 2024, Genmab’s Epkinly (epcoritamab), another CD20xCD3 BiTE, was approved in the same setting.

In patients who received AZD0486 doses of 2.4 mg or more in the trial (n = 27), the overall response rate (ORR) was 96%, and 85% had a complete response (CR). This outcome compares favourably to Epkinly’s phase I/II EPCORE trial and Lunsumio’s phase I/II GO29781 trial, which showed an ORR of 82% and 80% and a CR of 60% and 60% respectively. Cytokine release syndrome (CRS) is the main concern with many immunotherapies. 45% of patients who received a double step-up dose of AZD0486 experienced CRS, but all CRS events were grade 1. This result compares favourably to Epkinly, on which 60% of patients experienced CRS with 9% being grade 2 and 2% grade 3, but is similar to Lunsumio, which saw 44% of patients experience CRS with 1% of all patients experiencing grade 3 CRS.

AstraZeneca has commenced a phase II trial of AZD0486 in r/r FL, and if the results hold, it is likely to result in a first-in-class approval for a CD19xCD3 BiTE in this indication. During the same session at ASH 2024, Lunsumio and Epkinly both saw positive results in label expansion trials in FL. AstraZeneca also published positive results for AZD0486 in the more aggressive r/r diffuse large B-cell lymphoma setting. GlobalData’s analyst consensus forecast predicts that AZD0486 will reach $158 million in global sales by 2030, while Epkinly and Lunsumio will gain $2.4 billion and $949 million respectively. AZD0486 will likely catch up as banks release new forecasts after these positive results.