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DRUG:

pegenzileukin (SAR444245)

i
Other names: IBI-127, SAR'245, SAR444245, THOR-707, not alpha synthorin of IL-2, non alpha IL-2, THOR 707, recombinant human IL-2
Associations
Company:
Innovent Biologics, Sanofi
Drug class:
IL-2 stimulant
Related drugs:
Associations
22d
KEYNOTE-B71: A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Lung Cancer or Mesothelioma (Pegathor Lung 202) (clinicaltrials.gov)
P2, N=106, Terminated, Sanofi | Active, not recruiting --> Terminated; Early discontinuation based on strategic sponsor decision not driven by any safety concerns.
Trial termination
|
PD-L1 expression
|
Keytruda (pembrolizumab) • pegenzileukin (SAR444245)
1m
KEYNOTE-B78: A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Gastrointestinal Cancer (Master Protocol) (Pegathor Gastrointestinal 203) (clinicaltrials.gov)
P2, N=138, Terminated, Sanofi | Active, not recruiting --> Terminated; Early discontinuation based on strategic sponsor decision not driven by any safety concerns.
Trial termination
|
PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
|
Keytruda (pembrolizumab) • Erbitux (cetuximab) • pegenzileukin (SAR444245)
2ms
Enrollment change • Combination therapy
|
dexamethasone • pomalidomide • Sarclisa (isatuximab-irfc) • evorpacept (ALX148) • Blenrep (belantamab mafodotin-blmf) • SAR439459 • pegenzileukin (SAR444245)
2ms
A precision engineered interleukin-2 (IL-2) for bolstering CD8+ T- and NK-cell activity without eosinophilia and vascular leak syndrome in non-human primates. (PubMed, Cancer Res Commun)
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.
Journal
|
CD4 (CD4 Molecule) • IL2 (Interleukin 2)
|
pegenzileukin (SAR444245)
2ms
KEYNOTE-C39: A Study of SAR444245 With or Without Other Anticancer Therapies for the Treatment of Adults and Adolescents With Relapsed or Refractory B Cell Lymphoma (Master Protocol) [Pegathor Lymphoma 205] (clinicaltrials.gov)
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.
Trial completion date • Trial termination
|
Keytruda (pembrolizumab) • pegenzileukin (SAR444245)
2ms
HAMMER: A Study Evaluating Safety and Therapeutic Activity of THOR-707 in Adult Subjects With Advanced or Metastatic Solid Tumors (THOR-707-101) (clinicaltrials.gov)
P1/2, N=250, Active, not recruiting, Synthorx, Inc, a Sanofi company | Recruiting --> Active, not recruiting
Enrollment closed • Combination therapy • Metastases
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation
|
Keytruda (pembrolizumab) • Erbitux (cetuximab) • pegenzileukin (SAR444245)
3ms
Trial completion date
|
Keytruda (pembrolizumab) • Erbitux (cetuximab) • pegenzileukin (SAR444245)
6ms
Isatuximab in Combination With Novel Agents in RRMM - Master Protocol (clinicaltrials.gov)
P1/2, N=197, Recruiting, Sanofi | Trial completion date: Dec 2027 --> Mar 2028 | Trial primary completion date: Dec 2027 --> Jun 2027
Trial completion date • Trial primary completion date
|
dexamethasone • pomalidomide • Sarclisa (isatuximab-irfc) • evorpacept (ALX148) • Blenrep (belantamab mafodotin-blmf) • SAR439459 • pegenzileukin (SAR444245)
8ms
Trial completion date
|
Keytruda (pembrolizumab) • pegenzileukin (SAR444245)
9ms
Enrollment change
|
Libtayo (cemiplimab-rwlc) • pegenzileukin (SAR444245)
9ms
Enrollment change • Trial completion date • Metastases
|
PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
|
Keytruda (pembrolizumab) • Erbitux (cetuximab) • pegenzileukin (SAR444245)
9ms
Enrollment change
|
Keytruda (pembrolizumab) • pegenzileukin (SAR444245)
9ms
Enrollment change • Trial completion date
|
Keytruda (pembrolizumab) • Erbitux (cetuximab) • pegenzileukin (SAR444245)
10ms
Enrollment change • Trial completion date
|
PD-L1 expression
|
Keytruda (pembrolizumab) • pegenzileukin (SAR444245)
11ms
Isatuximab in Combination With Novel Agents in RRMM - Master Protocol (clinicaltrials.gov)
P1/2, N=197, Recruiting, Sanofi | N=123 --> 197 | Trial completion date: Nov 2028 --> Dec 2027 | Trial primary completion date: Nov 2028 --> Dec 2027
Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
|
pomalidomide • Sarclisa (isatuximab-irfc) • evorpacept (ALX148) • Blenrep (belantamab mafodotin-blmf) • SAR439459 • pegenzileukin (SAR444245)
12ms
Trial completion date • Metastases
|
PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
|
Keytruda (pembrolizumab) • Erbitux (cetuximab) • pegenzileukin (SAR444245)
over1year
Trial completion date • Metastases
|
PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
|
Keytruda (pembrolizumab) • Erbitux (cetuximab) • pegenzileukin (SAR444245)
over1year
SAR444245, A NON-ALPHA IL2, RESCUES CHRONIC ANTIGEN- AND CAR-DRIVEN T-CELL DYSFUNCTION (EHA 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
IO biomarker
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • CD22 (CD22 Molecule) • IL2 (Interleukin 2)
|
pegenzileukin (SAR444245)
over1year
HAMMER: A Study Evaluating Safety and Therapeutic Activity of THOR-707 in Adult Subjects With Advanced or Metastatic Solid Tumors (THOR-707-101) (clinicaltrials.gov)
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
Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation
|
pegenzileukin (SAR444245)
over1year
Joint modeling of safety and peripheral Mode-of-Action biomarkers to support RP2D identification in Phase 1 study of SAR444245 as monotherapy or combined with pembrolizumab in patients with advanced solid tumors (EADO 2023)
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.
P1 data • Clinical • PD(L)-1 Biomarker • Metastases
|
CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • IL2 (Interleukin 2)
|
GuardantOMNI
|
Keytruda (pembrolizumab) • Erbitux (cetuximab) • pegenzileukin (SAR444245)
over1year
Use of NK humanized mouse models for the in vivo evaluation of anti-tumor NK-cell therapies (AACR 2023)
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.
Preclinical
|
IL2 (Interleukin 2) • IL15 (Interleukin 15)
|
pegenzileukin (SAR444245)
over1year
Joint modeling of safety and peripheral mode-of-action (MoA) biomarkers to support RP2D identification in Phase 1 study of SAR444245 (SAR’245) as monotherapy (mono) or combined with pembrolizumab (pembro) in patients with advanced solid tumors (AACR 2023)
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.
P1 data • Clinical • PD(L)-1 Biomarker • Metastases
|
CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • IL2 (Interleukin 2)
|
GuardantOMNI
|
Keytruda (pembrolizumab) • pegenzileukin (SAR444245)
over1year
Trial completion date
|
Keytruda (pembrolizumab) • pegenzileukin (SAR444245)
over1year
Trial primary completion date • Metastases
|
PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
|
Keytruda (pembrolizumab) • Erbitux (cetuximab) • pegenzileukin (SAR444245)
almost2years
A Study of SAR444245 With or Without Other Anticancer Therapies for the Treatment of Adults and Adolescents With Relapsed or Refractory B Cell Lymphoma (Master Protocol) [Pegathor Lymphoma 205] (clinicaltrials.gov)
P2, N=50, Active, not recruiting, Sanofi | Trial completion date: May 2025 --> Sep 2023 | Trial primary completion date: Apr 2025 --> Aug 2023
Trial completion date • Trial primary completion date
|
CD19 (CD19 Molecule)
|
Keytruda (pembrolizumab) • pegenzileukin (SAR444245)
almost2years
A Study Evaluating Safety and Therapeutic Activity of THOR-707 in Adult Subjects With Advanced or Metastatic Solid Tumors (THOR-707-101) (clinicaltrials.gov)
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
Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation
|
pegenzileukin (SAR444245)
almost2years
Pegathor Lymphoma, a Phase 2 Study of SAR444245 As a Monotherapy or in Combination with Pembrolizumab for the Treatment of Adults and Adolescents with Relapsed or Refractory B Cell Lymphoma (ASH 2022)
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.
Clinical • P2 data • Combination therapy
|
CD19 (CD19 Molecule) • IL2RA (Interleukin 2 receptor, alpha)
|
Keytruda (pembrolizumab) • Proleukin (aldesleukin) • pegenzileukin (SAR444245)
2years
Enrollment closed • Metastases
|
PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
|
Keytruda (pembrolizumab) • Erbitux (cetuximab) • pegenzileukin (SAR444245)
2years
Enrollment closed
|
CD19 (CD19 Molecule)
|
Keytruda (pembrolizumab) • pegenzileukin (SAR444245)
over2years
THOR-707-101: A Study Evaluating Safety and Therapeutic Activity of THOR-707 in Adult Subjects With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
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
Trial completion date • Trial primary completion date • Combination therapy
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation
|
pegenzileukin (SAR444245)
over2years
Trial completion date • Trial primary completion date
|
CD19 (CD19 Molecule)
|
Keytruda (pembrolizumab) • pegenzileukin (SAR444245)
over2years
A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Gastrointestinal Cancer (Master Protocol) (Pegathor Gastrointestinal 203) (clinicaltrials.gov)
P2, N=280, Recruiting, Sanofi | Trial completion date: Jul 2023 --> Jan 2024 | Trial primary completion date: Jul 2023 --> Jan 2024
Trial completion date • Trial primary completion date
|
PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
|
Keytruda (pembrolizumab) • Erbitux (cetuximab) • pegenzileukin (SAR444245)
over2years
THOR-707-101: A Study Evaluating Safety and Therapeutic Activity of THOR-707 in Adult Subjects With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
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
Trial completion date • Trial primary completion date • Combination therapy
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation
|
pegenzileukin (SAR444245)
over2years
Enrollment change
|
CD19 (CD19 Molecule)
|
Keytruda (pembrolizumab) • pegenzileukin (SAR444245)
over2years
THOR-707-101: A Study Evaluating Safety and Therapeutic Activity of THOR-707 in Adult Subjects With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
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
Trial completion date • Trial primary completion date • Combination therapy
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation
|
pegenzileukin (SAR444245)
almost3years
Clinical • New P2 trial
|
MSI (Microsatellite instability)
|
Keytruda (pembrolizumab) • Erbitux (cetuximab) • pegenzileukin (SAR444245)
almost3years
Enrollment open
|
PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
|
Keytruda (pembrolizumab) • Erbitux (cetuximab) • pegenzileukin (SAR444245)
almost3years
Enrollment change • Combination therapy
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation
|
pegenzileukin (SAR444245)
3years
New P2 trial
|
PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
|
Keytruda (pembrolizumab) • Erbitux (cetuximab) • pegenzileukin (SAR444245)