SAR445877 / Sanofi - LARVOL DELTA

Initial safety and efficacy results from a first-in-human, phase 1/2 study of SAR445877, an anti-PD-1/IL-15 fusion protein, for patients with advanced solid tumors. (ASCO 2025) - P1/2 | "SAR445877 monotherapy demonstrated a tolerable safety profile and promising antitumor activity in pts with advanced solid tumors unresponsive or resistant to ICI."

Clinical • Metastases • P1/2 data • Genito-urinary Cancer • Hepatology • Infectious Disease • Melanoma • Metabolic Disorders • Oncology • Penile Cancer • Pneumonia • Respiratory Diseases • Sarcoma • Solid Tumor • Urothelial Cancer • CCL2 • CD8 • CXCL10 • CXCL8 • IFNG • IL10 • IL15 • IL2 • IL6 • TNFA

Multiomics preclinical characterization of SAR445877, an anti-PD-1 antibody-IL-15 mutein fusion protein with robust anti-tumor efficacy as monotherapy (AACR 2025) - "Together, these data elucidated the mechanism of anti-PD-1/IL15 showing contributions of NK and CD8 T cells associated with anti-tumor activity observed in mice. These findings suggest that mSAR'877 shows superior efficacy to single agent PD-1 or untargeted IL-15 in mouse tumor models.Note: all authors are employed by Sanofi and may hold stock and/or stock options"

IO biomarker • Monotherapy • Preclinical • Oncology • CD8 • IL15 • PD-L1

A First-in-human, Dose Escalation and Dose Expansion Study of SAR445877 in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=285 | Recruiting | Sponsor: Sanofi | Trial completion date: Mar 2028 ➔ Sep 2028

Combination therapy • Metastases • Monotherapy • Trial completion date • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MSI

SAR445877, an anti-PD-1 antibody-IL-15 mutein fusion protein restores function to exhausted T cells (AACR 2024) - "SAR'877 more potently induced proliferation and IFNγ and granzyme B production compared to anti-PD-1 and non-targeted IL15 mutein alone. Together, these results demonstrate that the PD-1 targeted IL15 mutein SAR'877 rescues the functional activity of chronically stimulated, exhausted T cells."

IO biomarker • Oncology • CD4 • CD8 • GZMB • HAVCR2 • IFNG • IL15

Spatiotemporal tumor immune modulation by localized delivery of cancer therapeutics using an implantable microdevice (AACR 2024) - "Other significant changes in immune cell markers include increases in CD45+, CD11b, CD11c, CD20 and CD27. In conclusion, we have shown that multiple oncology therapeutics can be screened simultaneously in a small number of mice using an implantable microdevice and data obtained with this technology is consistent with that obtained from traditional mouse tumor experiments.(1) Preclinical characterization of SAR445877, an anti-PD-1 antibody-IL-15 mutein fusion protein with robust anti-tumor efficacy as monotherapy and in combination with PD-L1 blockade."

IO biomarker • Oncology • CD20 • CD27 • CD8 • IL15 • ITGAM • ITGAX • PTPRC

A First-in-human, Dose Escalation and Dose Expansion Study of SAR445877 in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=240 | Recruiting | Sponsor: Sanofi | Trial completion date: Jun 2027 ➔ Mar 2028 | Trial primary completion date: Apr 2027 ➔ Jan 2027

Metastases • Monotherapy • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MSI

A phase 1/2, open label, first-in-human, dose escalation and expansion study of SAR445877 administered as monotherapy in adults with advanced solid tumors (SITC 2023) - P1/2 | "Dose escalation Part 1 is conducted in US, Spain and Netherlands. The study is enrolling participants."

Clinical • IO biomarker • Metastases • Monotherapy • P1/2 data • Oncology • Solid Tumor • CD8 • IL15 • IL2

A phase I/II, open label, first-in-human, dose escalation and expansion study of SAR445877 administered as monotherapy in adults with advanced solid tumors (ESMO 2023) - P1/2 | "The study is enrolling participants. Lu D et al, J Immunother Cancer (2020); 8(Suppl 3):573."

Clinical • IO biomarker • Metastases • Monotherapy • P1/2 data • Oncology • Solid Tumor • CD8 • IL15 • IL2

Preclinical characterization of SAR445877, an anti-PD-1 antibody-IL-15 mutein fusion protein with robust anti-tumor efficacy as monotherapy and in combination with PD-L1 blockade (AACR 2023) - P1/2 | "SAR445877 displayed a more potent antitumor efficacy than pembrolizumab. SAR445877 exhibited potent anti-tumor efficacy in PD-1 resistant preclinical model with good tolerability. These results support further evaluation of SAR445877 in a phase I clinical trial (ClinicalTrials.gov #NCT05584670)."

Combination therapy • IO biomarker • Monotherapy • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD4 • CD8 • IL15 • IL2

A First-in-human, Dose Escalation and Dose Expansion Study of SAR445877 in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=240 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MSI

A First-in-human, Dose Escalation and Dose Expansion Study of SAR445877 in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=240 | Not yet recruiting | Sponsor: Sanofi

Monotherapy • New P1/2 trial • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MSI