Biomarker Analysis of a Phase Ia/Ib Open-Label, Multicentre Study of Tiragolumab or Tiragolumab + Rituximab in Patients with Relapsed or Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (NHL)

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.1337-1337
• Main Authors: Ruppert, Shannon, Cuchelkar, Vaikunth, Meng, Raymond, Cho, Eunpi, Lear, Sean, Wong, Cheryl Victoria, Raval, Aparna, Nouet, Yann
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-147773

Background: NHL is the most common hematologic malignancy in adults, with follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL) being the most common subtypes. Despite therapeutic advances, most patients will experience relapse. New treatments are therefore needed to improve the outcome of patients with R/R NHL. T cell immunoreceptor with Ig and ITIM domains (TIGIT) is a well-known immune inhibitory receptor expressed on the surface of activated T cell and natural killer (NK)-cell subsets. TIGIT is expressed at higher levels than other checkpoints in intratumoral T cells in NHL and is highly correlated with PD-1 expression and T cell infiltration. This phase Ia/Ib trial (NCT04045028) evaluated the safety and pharmacokinetics of the anti-TIGIT agent, tiragolumab, alone or in combination with rituximab. Methods: Patients were recruited with histologically confirmed B-cell NHL whose disease has relapsed or failed to respond to ≥2 prior systemic treatment regimens, had ECOG PS 0-1, adequate hematologic and end organ function, and no history of CNS lymphoma. Patients received tiragolumab 600 mg IV Q3W with or without rituximab 375 mg/m 2 IV for the initial dose and 1400 mg SC rituximab/23400 U rHuPH20 QW for 8 doses. Here, we evaluate biomarker data collected from patients with R/R NHL dosed with tiragolumab as a single agent or in combination with rituximab via flow cytometry and IHC. Results: At data cut-off (July 2021), biomarker data had been collected from 14 patients with NHL. Baseline CD8 T cell density within the tumor region evaluated via IHC for these patients was between 500-6000 per mmA 2. In the peripheral blood of the 7 patients dosed with the combination of tiragolumab and rituximab, CD8 T cell expansion observed via absolute counts by flow cytometry was seen in 2 patients. Among the 7 patients, NK/NKT CD25 expression remained unchanged and a modest increase in NK CD69 expression was sustained above baseline in 1 patient. Overall, transient NK cell activation via increased CD69 expression was observed in 2 patients, which would be expected from the addition of rituximab. Increased PD-L1 expression was observed on multiple lymphocyte subsets in 4 of 7 patients in this cohort. Of the 7 patients who received single agent tiragolumab, trends in increased CD69 expression on NKs were observed in 4 patients and NK/NKT CD25 expression in 3 patients. A modest CD8 T cell activation, via increased CD69 expression, was observed in 2 patients, th