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DRUG:

RG6333

i
Other names: RG6333, RO7443904, RG-6333, RO-7443904, RG 6333, RO 7443904
Associations
Company:
Roche
Drug class:
CD19 inhibitor, CD28 agonist
Related drugs:
Associations
4ms
BP43131: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RO7443904 in Combination With Glofitamab in Participants With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (clinicaltrials.gov)
P1, N=53, Terminated, Hoffmann-La Roche | N=200 --> 53 | Trial completion date: Apr 2025 --> Jul 2024 | Recruiting --> Terminated | Trial primary completion date: Apr 2025 --> Jul 2024; The study was terminated due to sponsor portfolio re-alignment.
Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy
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CD20 (Membrane Spanning 4-Domains A1) • CD19 (CD19 Molecule)
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Gazyva (obinutuzumab) • Actemra IV (tocilizumab) • Columvi (glofitamab-gxbm) • RG6333
9ms
CD19-CD28: An affinity-optimized CD28 agonist for combination with glofitamab (CD20-TCB) as off-the-shelf immunotherapy. (PubMed, Blood)
We developed a bispecific CD19-targeted CD28 agonist (RG6333, CD19-CD28) to enhance the efficacy of glofitamab and similar TCBs by delivering signal 2 to tumor-infiltrating T cells. CD19-CD28 distinguishes itself from the superagonistic antibody TGN1412, as its activity requires the simultaneous presence of a TCR signal and CD19 target binding...Our findings highlight CD19-CD28 as a safe and highly efficacious off-the-shelf combination partner for glofitamab, similar TCBs, and other costimulatory agonists. CD19-CD28 is currently in a Phase 1 clinical trial in combination with glofitamab.
Journal • IO biomarker
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CD20 (Membrane Spanning 4-Domains A1)
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CD20 expression
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Columvi (glofitamab-gxbm) • RG6333 • theralizumab (TAB08)
1year
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RO7443904 in Combination With Glofitamab in Participants With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (clinicaltrials.gov)
P1, N=200, Recruiting, Hoffmann-La Roche | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Apr 2025
Trial completion date • Trial primary completion date • Combination therapy
|
CD20 (Membrane Spanning 4-Domains A1) • CD19 (CD19 Molecule)
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CD20 expression • CD19 expression
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Gazyva (obinutuzumab) • Actemra IV (tocilizumab) • Columvi (glofitamab-gxbm) • RG6333
2years
Phase 1 Study of CD19 Targeted CD28 Costimulatory Agonist in Combination with Glofitamab to Enhance T Cell Effector Function in Relapsed/Refractory B Cell Lymphoma (ASH 2022)
Across the different study parts, the treatment schedule is consistent with a single fixed dose of obinutuzumab (1000mg intravenously) given at least 3 days prior to glofitamab step up dosing (2.5/10/30mg)...Commencement of part 4, the expansion phase, including decision on the RO7443904 dose will be guided by a concerted review of safety, PK, and PD data from all dose escalation parts...Figure 1: Efficacy study in a disseminated DLBCL model in humanized NSG mice treated with monotherapy of glofitmab (0.15 mg/kg) or CD19-CD28 (1 mg/kg) as well as with a combination of both. The data suggest a strong anti-tumor effect when both agents are combined.
P1 data • Combination therapy
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CD19 (CD19 Molecule)
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Gazyva (obinutuzumab) • Columvi (glofitamab-gxbm) • RG6333
2years
RG6333 (CD19-CD28), a CD19-Targeted Affinity-Optimized CD28 Bispecific Antibody, Enhances and Prolongs the Anti-Tumor Activity of Glofitamab (CD20-TCB) in Preclinical Models (ASH 2022)
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).
Preclinical
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CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
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Gazyva (obinutuzumab) • Columvi (glofitamab-gxbm) • RG6333 • englumafusp alfa (RG6076) • theralizumab (TAB08)