Treeline and Roche Collaborate on Phase 1 Trial of BCL6 Degrader TLN-121 Combined with CD20×CD3 Bispecifics in B-Cell Lymphomas
核心洞察
Treeline Biosciences (搜索) and Roche signed a clinical trial collaboration and supply agreement to evaluate TLN-121 (搜索) combined with glofitamab and mosunetuzumab in B-cell lymphomas.
Treeline will sponsor a Phase 1 dose-escalation and expansion study, with Roche supplying the two CD20×CD3 T-cell-engaging bispecific antibodies for specific expansion cohorts.
Preclinical data show TLN-121 (搜索) enhances anti-tumor activity of both CD20×CD3 bispecifics and CD19 CAR-T therapy, with complete regressions observed in DLBCL mouse models.
Treeline Biosciences (搜索) has entered a clinical trial collaboration and supply agreement with Roche to evaluate TLN-121 (搜索), Treeline's BCL6 degrader, in combination with Roche's CD20×CD3 T-cell-engaging bispecific antibodies glofitamab (Columvi) and mosunetuzumab (Lunsumio) in separate combination cohorts for patients with B-cell lymphomas, including diffuse large B-cell lymphoma (搜索) (DLBCL).
Under the terms of the agreement, Treeline will sponsor and conduct the Phase 1 dose-escalation and expansion study, while Roche will supply glofitamab and mosunetuzumab for specific expansion cohorts. Treeline expects to initiate combination dosing for these expansion cohorts in the fourth quarter of 2026.
"CD20×CD3 T-cell-engaging bispecific antibodies such as glofitamab and mosunetuzumab have already transformed the treatment of B-cell lymphomas. We are excited to build on that progress in collaboration with Roche," said Josh Bilenker, M.D., co-founder and Chief Executive Officer of Treeline. "We have generated exciting preclinical data suggesting that TLN-121 (搜索) enhances the anti-tumor activity of both CD20×CD3 T-cell-engaging bispecific antibodies and CD19 CAR-T cell therapy. These results were predicted by published studies that showed BCL6 impairs the formation of an effective immune synapse between T- and B-cells."
Preclinical Rationale for the Combination
BCL6 is a transcriptional repressor that helps B-cell lymphomas evade immune attack by silencing genes important for effective T-cell interactions. In DLBCL cell lines, TLN-121 (搜索) restored expression of T-cell-recruiting cytokines and immune synapse genes.
Treeline investigated the combination of TLN-121 (搜索) and T-cell immunotherapies in DLBCL mouse xenograft models that responded suboptimally to either component as a single agent. In an aggressive DLBCL model supplemented with human T-cells, combining TLN-121 with a CD20×CD3 bispecific antibody produced complete regressions in four of six mice, compared with zero of six for TLN-121 alone and one of five for the antibody alone.
In an aggressive DLBCL xenograft model, combining TLN-121 (搜索) with CD19 CAR-T cells shrank tumors in four of six mice and completely regressed tumors in two of six, compared with no tumor shrinkage or regression in any mice for TLN-121 or the CD19 CAR-T alone.
Single-Agent Clinical Activity
TLN-121 (搜索) has demonstrated single-agent activity in an ongoing Phase 1 clinical trial, including complete responses, in late-line DLBCL, follicular lymphoma (搜索) (FL), and T follicular helper peripheral T-cell lymphoma (搜索) (TFH PTCL).
About Treeline Biosciences
Treeline is a clinical-stage biopharmaceutical company that matches compelling biological targets with proven drug approaches, including small molecule inhibitors, protein degraders, and targeted therapy antibody-drug conjugates, by integrating in-house R&D with leading-edge computational tools. The company's pipeline spans oncology, neurology and immunology.