englumafusp alfa (RG6076)

P1/2, N=498, Recruiting, Hoffmann-La Roche | Phase classification: P1 --> P1/2 | Trial completion date: Mar 2025 --> Mar 2027 | Trial primary completion date: Mar 2025 --> Mar 2027

In this study, we demonstrated the MoA of englumafusp alfa in R/R NHL and key PD effects in combination versus glofitamab monotherapy that will support optimal biological dose finding. Furthermore, the observed association between expansion of TEM cells in PB and changes in ctDNA dynamics at EoT, albeit preliminary, supports ctDNA as a marker for depth and durability of response. Overall, our PD and biomarker observations so far strengthen the rationale of combining glofitamab with englumafusp alfa to drive long-term responses in this heavily pre-treated NHL patient population.

After a single obinutuzumab dose (1000 mg), pts started glofitamab step up dosing receiving the first target dose of 30 mg on C2D1. 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.

P1, N=420, Recruiting, Hoffmann-La Roche | Trial completion date: Jan 2023 --> Mar 2025 | Trial primary completion date: Jan 2023 --> Mar 2025

In contrast, TGN1412, a CD28 superagonist antibody, induced strong T cell activation, proliferation and cytokine secretion in vitro and in huNSG. Scheduling studies with glofitamab and RG6333 in huNSG suggest a safe and potent treatment regimen by using Gazyva pre-treatment followed by a staggered infusion of glofitmab and RG6333 applying an interval of three days at the first treatment cycle...Interestingly, the alternation of RG6333 with an alternative 4-1BB costimulatory agent (RG6076; CD19-4-1BBL) completely prevented tumor relapse during glofitamab treatment for more than 120 days when RG6333 was given for the first treatment cycles followed by RG6076 at later cycles...Optimal scheduling including alternation of costimulatory bispecific antibodies suggest a powerful off-the-shelf T cell redirection approach as an alternative to CAR-T cell therapies. RG6333 is currently in a phase I, open-label, dose-escalation study in combination with glofitamab (NCT05219513).

P1 | N=362 | Recruiting | Sponsor: Hoffmann-La Roche | Phase classification: P1/2 --> P1

P1/2, N=362, Recruiting, Hoffmann-La Roche | Phase classification: P1 --> P1/2 | N=207 --> 362

RO7227166, a CD19 targeted 4-1BBL (CD137) costimulatory agonist has shown synergistic anti‑tumor activity when combined with glofitamab in preclinical models (fig 1). The maximum duration of the study for each participant will be up to 24 months in Part I (excluding survival follow-up) and up to 18 months in Part II and Part III. Tumor biopsies and peripheral blood biomarker analyses will be used to demonstrate MoA and proof of concept of an off the shelf flexible combination option providing signals 1 and 2.

P1; N=207; Recruiting; Sponsor:Hoffmann-La Roche