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779 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
  1. Martin Gutierrez1,
  2. Elena Garralda2,
  3. Emiliano Calvo3,
  4. Marloes van Dongen4,
  5. Ferry Eskens5,
  6. Morgan Finlay1,
  7. Fatima Menas6,
  8. Chen Zhu7,
  9. Meijing Wu7,
  10. Helene Guillemin-Paveau8,
  11. Giovanni Abbadessa7,
  12. Raymond Perez9,
  13. Ozlem Yildirim7 and
  14. Aung Naing10
  1. 1Hackensack Meridian Health, Hackensack, NJ, USA
  2. 2Vall D’ Hebron Institute of Oncology (VHIO), Barcelona, Spain
  3. 3START Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Madrid, Spain
  4. 4Antoni Van Leeuwenhoek, Netherlands Cancer Institute, Amsterdam, North Holland, Netherlands
  5. 5Erasmus University Medical Center, Rotterdam, South Holland, Netherlands
  6. 6Sanofi, Madrid, Madrid, Spain
  7. 7Sanofi, Cambridge, MA, USA
  8. 8Sanofi, Paris, Chilly-Mazarin, France
  9. 9Sanofi, Pennington, NJ, USA
  10. 10The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background SAR445877 is a fusion protein of high affinity anti-programmed cell death protein 1 (PD1) antibody combined with a detuned interleukin 15 (IL15) (complexed with IL15 receptor sushi domain). SAR445877, via its anti-PD1 moiety, binds to PD-1-expressing T and natural killer (NK) cells and potentially allows for a targeted expansion and activation of CD8+ T and NK cells expressing both PD1 and IL2/15Rβγ. Nonclinical studies have demonstrated the potential of SAR445877 as an immune-modulatory agent with good tolerability and therapeutic benefits in various neoplastic disease models including programmed cell death ligand 1 (PD-L1)/PD-L1 resistant models as a monotherapy.1 SAR445877 treatments in preclinical models showed increased cytotoxic immune cell recruitment to tumor microenvironment, prolonged survival, and tumor clearance.2

Methods This is a first in human, open-label, multicenter, dose escalation and expansion phase 1/2 study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor activities of SAR445877 administered intravenously as a single agent in adult participants with advanced unresectable or metastatic solid tumors (NCT05584670). The study is conducted in 2 parts. The Part 1 (dose escalation) will determine the maximum tolerated dose or maximum administered dose per occurrence of dose limiting toxicities in the first 28-days (cycle 1 and 2), recommended dose(s), and the overall safety and tolerability profile of SAR445877. A multicohort Part 2 (dose expansion) would assess the safety and preliminary efficacy of SAR445877 (2 dose levels in at least 1 indication, as applicable) and will include cohorts with advanced solid tumors regardless of the tumor proportion score/combined positive score and cohort with a negative expression of the PDL1. Approximately, 240 participants will be enrolled, of which nearly 75 participants will be enrolled in the Part 1 and 165 participants in the Part 2. Adverse effects will be assessed per National Cancer Institute, Common Terminology Criteria for Adverse Events version 5.0 and American Society for Transplantation and Cellular Therapy consensus grading. Tumor response will be determined according to Response Evaluation Criteria in Solid Tumors criteria. Dose escalation Part 1 is conducted in US, Spain and Netherlands. The study is enrolling participants.

Trial Registration NCT05584670


  1. Lu D, Polonskaya Z, Pei-Chang C, A novel human anti-PD1/IL15 bi-functional protein with robust anti-tumor activity and low systemic toxicity. J Immunother Cancer. 2020;8(Suppl 3):A1-A559

  2. Polonskaya Z, Pei-Chang C, Martimo S, MOA study of KD050, an anti-PD-1/IL-15 bi-functional antibody selectively targeted PD-1 positive tumor-infiltrating lymphocytes resulted in robust anti-tumor activity and low systemic toxicity. Cancer Res. 2022;82(Suppl 12):5215.

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