P2, N=106, Terminated, Sanofi | Active, not recruiting --> Terminated; Early discontinuation based on strategic sponsor decision not driven by any safety concerns.
P2, N=138, Terminated, Sanofi | Active, not recruiting --> Terminated; Early discontinuation based on strategic sponsor decision not driven by any safety concerns.
2 months ago
Trial termination
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PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
We have created a precisely pegylated IL-2 [SAR-444245 (SAR'245) or pegenzileukin, previously THOR- 707] designed for proliferation of target CD8+ T and NK cells for anti-cancer activity, with minimal expansion of anti-target regulatory CD4+ T cells (Tregs) that counter their action, or eosinophils that trigger vascular leak syndrome (VLS)...Ex vivo, SAR'245 enhanced T-cell receptor responses alone and in combination with PD-1 inhibitors without inducing cytokines associated with cytokine release syndrome or VLS. Results support the clinical development of SAR'245 as a drug candidate for the treatment of solid tumors, alone or in combination with PD-1 inhibitory agents.
P2, N=14, Terminated, Sanofi | Trial completion date: Jan 2025 --> Sep 2024 | Active, not recruiting --> Terminated; Early discontinuation based on strategic sponsor decision not driven by any safety concerns.
SAR444245 treatment of exhausted antigen-specific or CAR T cells restored functionality and alleviated T cell dysfunction in vitro and in vivo . These data suggest that SAR444245 rescue of CAR T cell exhaustion through maintenance of CAR T cell proliferative capacity, cytotoxicity, and polyfunctionality and provide rationale for future clinical study of SAR444245 with CAR T cells. Diffuse large B cell lymphoma, CAR-T, Cancer immunotherapy, Interleukin-2
Materials and SAR'245 was given IV as monotherapy Q2W [Cohort A], monotherapy Q3W [Cohort B] or Q3W + IV pembrolizumab 200 mg Q3W/400 mg Q6W [Cohort C] and Q3W + Cetuximab [Cohort D]. In early oncology studies, joint modeling using non-invasive biomarkers, including MoA and response biomarkers, and a safety profile can inform dose-response relationships and support RP2D selection. This innovative integrative modeling will guide clinical study design. Studies of SAR'245 that further explore the dosing and scheduling are on-going.
over 1 year ago
P1 data • Clinical • PD(L)-1 Biomarker • Metastases
We show that SAR444245 (non-alpha IL2) can activate huNK cells in vivo in all developed huIL-15 transgenic models and confirmed the minimal effective dose by flow-cytometry PD studies. We show the efficacy of both reference and internal ADCC-enhanced antibodies in disseminated tumor models in our humanized huIL-15 transgenic mice. In addition, we performed a deep characterization of huNK cells in huIL-15 transgenic models, using a 28-color flow cytometry panel centered on NK cell biology and profiled them transcriptionally by single cell RNA Seq in a disseminated B-cell lymphoma model.Overall, we have developed robust models sustaining fully functional huNK cells that can be proficiently recruited in vivo by various NK-based therapeutics and can be used to evaluate the efficacy of combination therapies.
In early oncology studies, joint modeling using non-invasive biomarkers, including MoA and response biomarkers, and a safety profile can inform dose-response relationships and support RP2D selection. This innovative integrative modeling will guide clinical study design. Studies of SAR’245 that further explore the dosing and scheduling are on-going.
over 1 year ago
P1 data • Clinical • PD(L)-1 Biomarker • Metastases
P1/2, N=300, Recruiting, Synthorx, Inc, a Sanofi company | Trial completion date: Aug 2023 --> Mar 2024 | Trial primary completion date: Aug 2023 --> Mar 2024
almost 2 years ago
Trial completion date • Trial primary completion date • Combination therapy • Metastases
In animal models, SAR444245 showed anti-tumor benefits, and with no severe side effects, both as a single agent as well as when combined with anti-PD1 compared with historical data from aldesleukin. Both primary endpoints are based on Lugano response criteria 2014. The main secondary endpoints include safety and other efficacy assessments.