AZD0486

Median prior lines of therapy was 3 (range 2–12), 18 (38%) pts received prior lenalidomide–based therapy, 7 (15%) pts received prior chimeric antigen receptor T-cell therapy (CAR-T), and 4 (9%) received prior CD20 TCE therapy. AZD0486 offers high response rates in pts with R/R FL at target doses ≥2.4 mg. Responses were durable. 2SUD allows safe administration of the target dose up to at least 15 mg.

P3, N=1005, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

P1/2, N=180, Not yet recruiting, AstraZeneca

P3, N=1005, Not yet recruiting, AstraZeneca

P1, N=116, Recruiting, AstraZeneca | N=206 --> 116

P2, N=240, Not yet recruiting, AstraZeneca

P1, N=206, Recruiting, AstraZeneca | N=116 --> 206

P1/2, N=120, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

P1, N=116, Recruiting, AstraZeneca | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2025 --> Oct 2026

P1/2, N=120, Not yet recruiting, AstraZeneca

P1, N=116, Recruiting, AstraZeneca | Trial completion date: May 2024 --> Oct 2025 | Trial primary completion date: Aug 2023 --> Oct 2025

AZD0486 (formerly TNB-486) is an active treatment in patients with advanced R/R B-NHL and has a predictable safety profile characterized by mainly low-grade AEs and fully transient and reversible CRS/ICANS events. The 2 SUD schedule reduced the overall rate of low grade CRS and ICANS (Grade 1-2) and abrogated Grade 3 events further improving the risk/benefit profile of AZD0486. Dose escalation is ongoing to identify the RP2D.

Background: Despite the groundbreaking introduction of rituximab for the treatment of diffuse large B cell lymphoma (DLBCL), approximately 30% of the patients ultimately experience refractory / relapse (R/R) disease and so far myriads attempts to improve survival outcomes have not yielded firm positive results...To mitigate the risk of glofitamab associated cytokine release syndrome, obinutuzumab premedication and cycle 1 step-up dosing was implemented...One patient with a previous history of prior COVID19 infection after TNB-486 (CD19/CD3 bispecific) clinical trial, despite receiving vaccination prior to this study enrollment, experienced COVID19 reactivation after cycle 1... Glofitamab, poseltinib and lenalidomide (GPL) is promising combination for thetreatment of R/R DLBCL. (Table) Refractory, DLBCL, Bispecific

TNB-486 induces high complete remission rates during early phase dose escalation. With limited follow-up, responses appear durable in heavily pretreated FL pts, with a manageable safety profile. Dose escalation is ongoing to identify the RP2D.