pegenzileukin (SAR444245)

P1/2, N=46, Terminated, Sanofi | Active, not recruiting --> Terminated; Early discontinuation based on strategic sponsor decision not driven by any safety concerns

P2, N=59, Terminated, Sanofi | Active, not recruiting --> Terminated; Early discontinuation based on strategic sponsor decision not driven by any safety concerns.

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.

P1/2, N=258, Recruiting, Sanofi | N=197 --> 258

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.

P1/2, N=250, Active, not recruiting, Synthorx, Inc, a Sanofi company | Recruiting --> Active, not recruiting

P2, N=59, Active, not recruiting, Sanofi | Trial completion date: Feb 2025 --> Nov 2024

P1/2, N=197, Recruiting, Sanofi | Trial completion date: Dec 2027 --> Mar 2028 | Trial primary completion date: Dec 2027 --> Jun 2027

P2, N=14, Active, not recruiting, Sanofi | Trial completion date: Sep 2024 --> Jan 2025

P1/2, N=46, Active, not recruiting, Sanofi | N=80 --> 46

P2, N=138, Active, not recruiting, Sanofi | N=280 --> 138 | Trial completion date: Mar 2024 --> Sep 2024

P2, N=14, Active, not recruiting, Sanofi | N=50 --> 14

P2, N=59, Active, not recruiting, Sanofi | N=120 --> 59 | Trial completion date: Aug 2024 --> Feb 2025

P2, N=107, Active, not recruiting, Sanofi | N=160 --> 107 | Trial completion date: Feb 2024 --> Jan 2025

P1/2, N=197, Recruiting, Sanofi | N=123 --> 197 | Trial completion date: Nov 2028 --> Dec 2027 | Trial primary completion date: Nov 2028 --> Dec 2027

P2, N=280, Active, not recruiting, Sanofi | Trial completion date: Sep 2023 --> Mar 2024

P2, N=280, Active, not recruiting, Sanofi | Trial completion date: Jan 2024 --> Sep 2023

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

P1/2, N=300, Recruiting, Synthorx, Inc, a Sanofi company | Trial completion date: Mar 2024 --> Apr 2026 | Trial primary completion date: Mar 2024 --> Apr 2026

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.

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.

P2, N=50, Active, not recruiting, Sanofi | Trial completion date: Sep 2023 --> Sep 2024

P2, N=280, Active, not recruiting, Sanofi | Trial primary completion date: Jan 2024 --> Jul 2023

P2, N=50, Active, not recruiting, Sanofi | Trial completion date: May 2025 --> Sep 2023 | Trial primary completion date: Apr 2025 --> Aug 2023

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

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.

P2, N=280, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting

P2, N=50, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting

P1/2, N=300, Recruiting, Synthorx, Inc, a Sanofi company | Trial completion date: Apr 2023 --> Aug 2023 | Trial primary completion date: Apr 2023 --> Aug 2023

P2, N=50, Recruiting, Sanofi | Trial completion date: Sep 2025 --> Apr 2025 | Trial primary completion date: Aug 2025 --> Mar 2025

P2, N=280, Recruiting, Sanofi | Trial completion date: Jul 2023 --> Jan 2024 | Trial primary completion date: Jul 2023 --> Jan 2024

P1/2, N=300, Recruiting, Synthorx, Inc, a Sanofi company | Trial completion date: Dec 2022 --> Apr 2023 | Trial primary completion date: Dec 2022 --> Apr 2023

P2, N=50, Recruiting, Sanofi | N=25 --> 50

P1/2, N=300, Recruiting, Synthorx, Inc, a Sanofi company | Trial completion date: Apr 2022 --> Dec 2022 | Trial primary completion date: Apr 2022 --> Dec 2022

P2, N=60, Ongoing, Sanofi-Aventis Recherche & Développement

P2, N=350, Ongoing, Sanofi-Aventis Recherche & Developpement

P2, N=280, Recruiting, Sanofi | Not yet recruiting --> Recruiting

P1/2, N=300, Recruiting, Synthorx, Inc, a Sanofi company | N=200 --> 300