P1, N=50, Active, not recruiting, TG Therapeutics, Inc. | Trial completion date: Dec 2023 --> Mar 2024 | Trial primary completion date: Dec 2023 --> Mar 2024
9 months ago
Trial completion date • Trial primary completion date
Cell response to TG-1801 alone or combined with the U2 regimen associating ublituximab to the PI3Kδ inhibitor umbralisib, was analyzed by proliferation assay, western blot, transcriptomic analysis (qPCR array and RNA sequencing followed by gene set enrichment analysis) and/or quantification of antibody-dependent cell death (ADCC) and antibody-dependent cell phagocytosis (ADCP). Genetic depletion and pharmacological inhibition of GPR183 impaired ADCP initiation, cytoskeleton remodeling and cell migration in 2D and 3D spheroid B-NHL co-cultures, and disrupted macrophage-mediated control of tumor growth in B-NHL CAM xenografts. Altogether, our results support a crucial role for GPR183 in the recognition and elimination of malignant B cells upon concomitant targeting of CD20, CD47 and PI3Kδ, and warrant further clinical evaluation of this triplet regimen in B-NHL.
Combination of CD47 blockade with the anti-CD20 antibody rituximab has resulted in encouraging clinical activity (Advani 2018), and CD19 is also an established target of multiple B-NHL therapies...A 3+3 design was also utilized to evaluate two dose levels of TG-1801 (300 mg and 400 mg) with a standard dose of ublituximab (900 mg)... TG-1801 monotherapy and combination therapy demonstrates clinical activity, particularly in relapsed and refractory DLBCL, with an acceptable preliminary safety profile. This study (NCT03804996) has completed enrollment.
The study described the mechanisms afforded by the CD47xCD19 bispecific antibody, NI-1701, at controlling tumor growth in lymphoma mouse model. NI-1701 is currently being evaluated in a Phase I clinical trial for the treatment of refractory or relapsed B-cell lymphoma (NCT04806035).
over 2 years ago
Preclinical • Journal
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CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • SIRPA (Signal Regulatory Protein Alpha)
The latter is also used in our CD47xCD19 bispecific antibody NI-1701/TG-1801, currently in phase I clinical trials (NCT03804996, NCT04806035)...NI-2601 demonstrated effective blockade of PD-1/PD-L1 interaction, and T-cell activation in vitro, similar to the anti-PD-L1 clinical benchmarks atezolizumab and avelumab...Thus, NI-2601 is able to harness Fc-effector function to eliminate PD-L1-positive tumor cells while sparing PD-L1-negative cells, such as RBC or platelets. Pharmacokinetic and tolerability studies in non-human primate are planned for 2022.
over 2 years ago
PD(L)-1 Biomarker • IO biomarker
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CD47 (CD47 Molecule) • SIRPA (Signal Regulatory Protein Alpha)