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
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
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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