Combining Cd19‐4‐1bbl (Ro7227166) With Glofitamab Is Safe and Shows Early Efficacy in Patients Suffering From Relapsed or Refractory B‐cell Non‐hodgkin Lymphoma

Martin Hutchings; Michael Dickinson; Carmelo Carlo‐Stella; Franck Morschhauser; Francesc Bosch; Giuseppe Gritti; William Townsend; Nancy L. Bartlett; Guillaume Cartron; Hervé Ghesquières; Roch Houot; Harriet S. Walter; Fritz Offner; Anita Vedel Christiansen; Natalie Dimier; C. Jamois; Emily Harrop; Sylvia Herter; Gabriele Hölzlwimmer; Koorosh Korfi; Jason Luong; Claudia Mueller; Sarah Louise Mycroft; Matt Whayman; Isabel Prieto; Daria Rukina; Katharina Lechner

doi:10.1002/hon.3163_91

Key Points

To evaluate the safety, pharmacokinetics, and pharmacodynamics of combining the CD19-directed costimulatory bispecific antibody RO7227166 with glofitamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma.
Administered RO7227166 in combination with glofitamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma.
Evaluated pharmacokinetics across dose levels, including doses of 22 mg or greater.
Analyzed pharmacodynamic changes in CD8-positive and effector memory T-cell subsets and monitored safety profiles for additive toxicities.
RO7227166 exposure increased in a near dose-proportional manner at doses of 22 mg or greater.
Pharmacodynamic analysis demonstrated an expansion of primed and activated CD8-positive T cells and effector memory T cells, alongside a reduction in exhausted T-cell phenotypes.
Combination safety was primarily driven by glofitamab, with no additive safety signals detected from RO7227166.

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Implication

Clinical trial reveals safety and T-cell activation with RO7227166 plus glofitamab in refractory B-cell lymphoma, indicating a viable dual-immunotherapy strategy.

Abstract

RO7227166 exposure increased in an almost dose proportional manner for doses ≥22 mg.Furthermore, pharmacodynamic analysis showed expansion of primed and activated CD8, and effector memory T-cells, with a reduction of exhausted T cell phenotypes.Conclusions: Glofitamab can be safely combined with a costimulatory bispecific antibody (RO7227166) in R/R B-NHL.The safety profile of the combination was mainly driven by glofitamab and we did not detect an additive safety signal from RO7227166.

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Hutchings et al. (2023) studied this question.

synapsesocial.com/papers/6aa4c1a5bb06bc417bf2d007 https://doi.org/10.1002/hon.3163_91

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Combining Cd19‐4‐1bbl (Ro7227166) With Glofitamab Is Safe and Shows Early Efficacy in Patients Suffering From Relapsed or Refractory B‐cell Non‐hodgkin Lymphoma

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Cite This Study

Combining Cd19‐4‐1bbl (Ro7227166) With Glofitamab Is Safe and Shows Early Efficacy in Patients Suffering From Relapsed or Refractory B‐cell Non‐hodgkin Lymphoma

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