PD-L1

The Role of PD-L1 Pathway Inhibition in Immunotherapy

PD-L1

PD-L1 blockade reverses T-cell exhaustion, reinvigorating antitumor activity3-7

PD-L1 and PD-1 play different roles in immune regulation and T-cell activation PD-1: programmed cell death-1; PD-L1: programmed cell death ligand-1; CD80: cluster of differentiation 80; CD28: cluster of differentiation 28

Disrupting the PD-L1 pathway

TAKE A DEEPER LOOKat PD-L1 and PD-1

LEARN MORE about how testing for PD-L1 may help inform treatment decisions

DURVALUMAB

Durvalumab (anti-PD-L1 antibody)

  • Durvalumab (MEDI4736) blocks PD-L1 binding to PD-1 and CD80. It is being investigated alone and in combination with tremelimumab for its potential effects on NSCLC, HNSCC, bladder cancer, and other tumor types.10-14

VIEW the full list of clinical trials with durvalumab

PD-1=programmed cell death-1; PD-L2=programmed cell death ligand-2; NSCLC=non-small cell lung cancer; HNSCC=head and neck squamous cell carcinoma; CTLA-4= cytotoxic T-lymphocyte–associated antigen 4.

References

1. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252-264. 2. Haile ST, Dalal SP, Clements V, et al. Soluble CD80 restores T cell activation and overcomes tumor cell programmed death ligand 1-mediated immune suppression. J Immunol. 2013;191:2829-2836. 3. Stewart R, Morrow M, Hammond SA, et al. Identification and characterization of MEDI4736, an antagonistic anti–PD-L1 monoclonal antibody. Cancer Immunol Res. 2015;3:1052-1062. 4. Ibrahim R, Stewart R, Shalabi A. PD-L1 blockade for cancer treatment: MEDI4736. Semin Oncol. 2015;42:474-483. 5. Sznol M, Chen L. Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer. Clin Cancer Res. 2013;19:1021-1034. 6. Chen DS, Irving BA, Hodi FS. Molecular pathways: next-generation immunotherapy—inhibiting programmed death-ligand 1 and programmed death-1. Clin Cancer Res. 2012;18:6580-6587. 7. Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. 2013;13:227-242. 8. Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ. Programmed death-1 ligand 1 interacts specifically with the B7.1 costimulatory molecule to inhibit T cell responses. Immunity. 2007;27:111-122. 9. Intlekofer AM, Thompson CB. At the bench: preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy. J Leukoc Biol. 2013;94:25-39. 10. Segal NH, Ou S-HO, Balmanoukian AS, et al. Safety and efficacy of MEDI4736, an anti-PD-L1 antibody, in patients from a squamous cell carcinoma of the head and neck (SCCHN) expansion cohort. Poster presented at ASCO 2015. Poster 3011. 11. Antonia S, Goldberg SB, Balmanoukian A, et al. Safety and antitumor activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Lancet Oncol. 2016;17:299-308. 12. Gilbert J, Le Tourneau C, Mehanna H, et al. Phase II, randomized, open-label study of durvalumab (MEDI4736) or tremelimumab monotherapy, or durvalumab + tremelimumab, in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): CONDOR. J Immunother Cancer. 2015;3(suppl 2):P152. 13. National Institutes of Health: ClinicalTrials.gov. Study of MEDI4736 with or without tremelimumab versus standard care of chemotherapy in urothelial cancer. https://clinicaltrials.gov/ct2/show/NCT02516241?term=durvalumab+bladder+tremelimumab&rank=1. Accessed July 3, 2017. 14. AstraZeneca. Clinical trials appendix Q1 2017 results update. https://www.astrazeneca.com/content/dam/az/PDF/2017/QR1/Q1_2017_Results_Clinical_Trial_Appendix.pdf. Accessed May 10, 2017.

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