IMMUNO-ONCOLOGY

The PD-L1 pathway

The binding of PD-L1 to PD-1 results in T-cell suppression and inactivation. In cancer, PD-1/PD-L1 signaling serves as a mechanism for tumors to evade an immunologic response, thus promoting cancer progression and survival.1,2

Avelumab - anti-PD-L1 mAb

Description and Mechanism of Action:

Avelumab is a fully human anti-PD-L1 IgG1 monoclonal antibody. By inhibiting PD-L1 interactions, avelumab is thought to enable the activation of T-cells and adaptive immune responses. By retaining a native Fc-region, avelumab is designed to engage the innate immune system and induce antibody-dependent cellular cytotoxicity (ADCC).1,3

Avelumab is thought to selectively bind PD-L1, inhibiting PD-1/PD-L1 interactions and promoting a T-cell mediated antitumor response. Preclinical models also suggest that innate effector function may contribute to antitumor activity.1,4,5

The PD-L1 Pathway

Based on preclinical data in murine models; may not necessarily correlate with clinical outcomes.

Areas of interest:

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TRIALS

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Avelumab is being developed and commercialized in a strategic global alliance between EMD Serono and Pfizer Inc.

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Pathways Under Investigation

TIGIT

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TGF-β

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Abbreviations:
Fc, fragment crystallizable; FcγR, receptor for Fc part of IgG; IgG1, immunoglobulin G1; mAb, monoclonal antibody; NK, natural killer; PD-1, programmed death 1; PD-L1, programmed death-ligand 1; TGF-β, transforming growth factor-β; TIGIT, T-cell immunoglobulin and ITIM domain.

References:

  1. Heery CR, O'Sullivan-Coyne G, Madan RA, et al. Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial. Lancet Oncol. 2017;18(5):587-598.
  2. Akinleye A, Rasool Z. Immune checkpoint inhibitors of PD-L1 as cancer therapeutics. J Hematol Oncol. 2019;12(1):92.
  3. Chin K, Chand VK, Nuyten DSA. Avelumab: clinical trial innovation and collaboration to advance anti-PD-L1 immunotherapy. Ann Oncol. 2017;28(7):1658-1666.
  4. Boyerinas B, Jochems C, Fantini M, et al. Antibody-dependent cellular cytotoxicity activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells. Cancer Immunol Res. 2015;3(10):1148-1157.
  5. Gulley JL, Rajan A, Spigel DR, et al. Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial. Lancet Oncol. 2017;18(5):599-610.

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