Safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of PF 06801591, an anti-PD1 antibody administered intravenously (IV) or subcutaneously (SC)

Hu‐Lieskovan, Siwen; Johnson, Melissa M.; Braiteh, Fadi; Grilley‐Olson, Juneko E.; Chou, Jeffrey; Davda, Jasmine; Jin, Bo; Forgie, Alison; Rassam, D.; Youssef, Sawsan

doi:10.1093/annonc/mdx376.048

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“…Sasanlimab (PF-06801591) is a humanized, immunoglobulin G4 monoclonal antibody that binds to the PD-1 receptor with high affinity and blocks its interaction with PD-1 ligands [13][14][15]. Clinical findings from the firstin-human, dose-escalation, phase I study (B8011001) of sasanlimab administered intravenously (IV) or subcutaneously (SC) in patients with locally advanced or metastatic solid tumors showed that treatment was well tolerated at all the investigated dose levels (0.5-10 mg/kg IV every 3 weeks (q3w) and 300 mg SC every 4 weeks (q4w)) [14,15]. Full PD-1 receptor occupancy in peripheral CD8 + T cells was also observed at all dose levels, independent of baseline PD-1 expression levels [15].…”

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confidence: 99%

Association of Tumor Mutational Burden and Immune Gene Expression with Response to PD-1 Blockade by Sasanlimab Across Tumor Types and Routes of Administration

et al. 2021

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Background Sasanlimab is a monoclonal antibody that binds to the programmed cell death receptor 1 (PD-1). Anti-PD-1 monoclonal antibodies have improved patient clinical outcomes; however, not all treated patients derive clinical benefit. Further insights on potential biomarkers beyond PD-L1 expression levels would help to identify the patients most likely to respond to treatment. Objective This study evaluated tumor biopsies from patients treated with intravenous or subcutaneous sasanlimab to identify biomarkers of response and characterize pharmacodynamic activity. Methods Anti-PD-1/PD-ligand 1 (PD-L1)-naive patients with advanced solid tumors received sasanlimab intravenously at 1, 3, or 10 mg/kg every 3 weeks (n = 23) or subcutaneously at 300 mg every 4 weeks (n = 15). Best tumor percentage change from baseline was determined by RECIST. Whole-exome DNA and RNA sequencing were performed in tumor samples collected from treated patients at protocol-defined timepoints. PD-L1 and CD8 protein expression were evaluated in tumor biopsies by immunohistochemistry. Associations with response were assessed by linear regression analysis. Results Baseline tumor mutational burden (TMB), as well as PD-L1 and CD8 expression, were significantly associated with response to sasanlimab across the multiple dose levels, routes of administration, and range of tumor types evaluated. TMB is an independent biomarker from the various tumor inflammatory genes and signatures evaluated. Gene set enrichment analysis showed that higher baseline expression levels of genes related to the interferon-γ and PD-1 signaling pathways and the cell cycle were significantly associated with response to sasanlimab across tumor types. No differences were observed between routes of administration with regard to response to sasanlimab for the biomarkers of interest (TMB, PD-L1, CD8, and interferon-γ signature). Evaluation of pharmacodynamic changes showed increased tumor expression of genes enriched in adaptive immune response pathways. Conclusions Our findings indicate an active, immunomodulatory mechanism for the anti-PD-1 antibody sasanlimab across different tumor types and routes of administration. Trial Registration ClinicalTrials.gov identifier NCT02573259; registered October 2015.

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