Drugs

, Volume 77, Issue 12, pp 1369–1376

Durvalumab: First Global Approval

AdisInsight Report
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Abstract

Intravenous durvalumab (Imfinzi™; AstraZeneca) is a fully human monoclonal antibody that blocks programmed cell death ligand-1 binding to its receptors (PD-1 and CD80), resulting in enhanced T-cell responses against cancer cells. The US FDA has granted durvalumab accelerated approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. Durvalumab ± tremelimumab is under phase III clinical trials in urothelial carcinoma, non-small cell lung cancer, small cell lung cancer and head and neck squamous cell carcinoma. The drug is also being evaluated in phase I or II clinical trials in a wide range of solid tumours and haematological malignancies. This article summarizes the milestones in the development of durvalumab leading to this first approval for urothelial carcinoma.

References

  1. 1.
    Ibrahim R, Stewart R, Shalabi A. PD-L1 blockade for cancer treatment: MEDI4736. Semin Oncol. 2015;42(3):474–83.CrossRefPubMedGoogle Scholar
  2. 2.
    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(9):1052–62.CrossRefPubMedGoogle Scholar
  3. 3.
    Imfinzi™ (durvalumab): US prescribing information. 2017. https://www.fda.gov. Accessed 24 May 2017.
  4. 4.
    AstraZeneca. Durvalumab granted Breakthrough Therapy designation by US FDA for treatment of patients with PD-L1 positive urothelial bladder cancer [media release]. 17 Feb 2016. http://www.astrazeneca.com.
  5. 5.
    AstraZeneca. US FDA accepts first biologics license application for AstraZeneca’s durvalumab in bladder cancer [media release]. 9 Dec 2016. http://www.astrazeneca.com.
  6. 6.
    AstraZeneca. MedImmune and Mirati Therapeutics partner on immuno-oncology combination in lung cancer [media release]. 5 Aug 2015. www.astrazeneca.com.
  7. 7.
    Peregrine Pharmaceuticals. AstraZeneca and Peregrine Pharmaceuticals expand ongoing immuno-oncology collaboration to include phase II lung cancer combination clinical trial [media release]. 15 Oct 2015. http://www.peregrineinc.com.
  8. 8.
    Eli Lilly. Lilly and AstraZeneca expand immuno-oncology research collaboration with new combinations [media release]. 22 Oct. 2015. http://www.lillyoncology.com.
  9. 9.
    Celgene International SARL. Celgene corporation enters into strategic immuno-oncology collaboration with Astrazeneca to develop PD-L1 inhibitor program for patients with serious blood cancers [media release]. 24 April 2015. http://www.celgene.com.
  10. 10.
    AstraZeneca. AstraZeneca PLC first quarter results 2015 [media release]. 24 Apr 2015. http://www.astrazeneca.com.
  11. 11.
    Innate Immune. Innate Pharma and AstraZeneca announce global co-development and commercialisation agreement for IPH2201 in immuno-oncology [media release]. 24 April 2015. http://www.innate-pharma.com.
  12. 12.
    AstraZeneca, Pharmacyclics, Janssen Research Development. AstraZeneca, Pharmacyclics and Janssen partner on immuno-oncology combination trials with Imbruvica® for hematologic cancers [media release]. 4 Nov. 2014. http://www.astrazeneca.com.
  13. 13.
    AstraZeneca. Medimmune and Immunocore announce new collaboration to conduct immuno- oncology combination trials in melanoma [media release]. 16 April 2015. http://www.astrazeneca.com.
  14. 14.
    Advaxis. Advaxis and MedImmune partner on immuno-oncology combination clinical trial [media release]. 22 July 2014. http://www.advaxis.com.
  15. 15.
    Kyowa Hakko Kirin. Kyowa Hakko Kirin and AstraZeneca partner on immuno-oncology clinical study [media release]. 30 July2014. http://www.kyowa-kirin.com.
  16. 16.
    Higgs BW, Morehouse C, Streicher K, et al. Relationship of baseline tumoral IFNγ mRNA and PD-L1 protein expression to overall survival in durvalumab-treated NSCLC patients [abstract no. 3036]. J Clin Oncol. 2016;34(Suppl):3036.Google Scholar
  17. 17.
    Antonia S, Goldberg SB, Balmanoukian A, et al. Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Lancet Oncol. 2016;17(3):299–308.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Hamid O, Chow LQ, Sanborn RE, et al. Combination of MEDI0680, an anti-PD-1 antibody, with durvalumab, an anti-PD-L1 antibody: a phase 1, open-label study in advanced malignancies [abstract no. 1050PD]. Ann Oncol. 2016;27(Suppl 6). doi:10.1093/annonc/mdw378.05.
  19. 19.
    Yeh T, Jacobs V, Angell H, et al. Inhibition of pEGFR in paired tumour biopsies from TKI treatment-naive EGFR mutant NSCLC patients treated with gefitinib (EGFR inhibitor) or gefitinib in combination with durvalumab (anti-PD-L1) [abstract no. 60PD]. J Thorac Oncol. 2016;11(Suppl 4):S80–1.CrossRefPubMedGoogle Scholar
  20. 20.
    Song X, Pak M, Chavez C, et al. Population pharmacokinetics of MEDI4736, a fully human antiprogrammed death ligand 1 (PD-L1) monoclonal antibody, in patients with advanced solid tumors [abstract no. 203]. Eur J Cancer. 2015;51(Suppl 3):S28.CrossRefGoogle Scholar
  21. 21.
    Gibbons DL, Chow LQ, Kim DW, et al. Efficacy, safety and tolerability of MEDI4736 (durvalumab [D]), a human IgG1 anti-programmed cell death-ligand-1 (PD-L1) antibody, combined with gefitinib (G): a phase I expansion in TKI-naive patients (pts) with EGFR mutant NSCLC [abstract no. 57O]. J Thorac Oncol. 2016;11(Suppl 4):S79.CrossRefPubMedGoogle Scholar
  22. 22.
    Hahn NM, Powles T, Massard C, et al. Updated efficacy and tolerability of durvalumab in locally advanced or metastatic urothelial carcinoma (UC) [abstract no. 4525 plus poster]. J Clin Oncol. 2017;35(Suppl):286.Google Scholar
  23. 23.
    AstraZeneca. Imfinzi™ (durvalumab) significantly reduces the risk of disease worsening or death in the phase III PACIFIC trial for stage III unresectable lung cancer [media release]. 15 May 2017. https://www.astrazeneca-us.com.
  24. 24.
    Antonia SJ, Brahmer JR, Khleif S, et al. Phase 1/2 study of the safety and clinical activity of durvalumab in patients with non-small cell lung cancer (NSCLC) [abstract no. 1216PD]. Ann Oncol. 2016;27(Suppl 6). doi:10.1093/annonc/mdw383.16.
  25. 25.
    Antonia SJ, Kim SW, Spira AI, et al. Safety and clinical activity of durvalumab (MEDI4736), an anti-PD-LI antibody, in treatment-naive patients with advanced non-small-cell lung cancer [abstract no. 9029]. J Clin Oncol. 2016;34(Suppl):8032.Google Scholar
  26. 26.
    Segal NH, Ou SHI, Balmanoukian AS, et al. Updated safety and efficacy of durvalumab (MEDI4736), an anti-PD-L 1 antibody, in patients from a squamous cell carcinoma of the head and neck (SCCHN) expansion cohort [abstract no. 949O]. Ann Oncol. 2016;27(Suppl 6). doi:10.1093/annonc/mdw376
  27. 27.
    Reardon DA, Kaley TJ, Dietrich J, et al. Phase 2 study to evaluate safety and efficacy of MEDI4736 (durvalumab [DUR]) in glioblastoma (GBM) patients: an update [abstract no. 2042 plus poster]. J Clin Oncol. 2017;35(Suppl):TPS2080.Google Scholar
  28. 28.
    Iguchi H, Nogami N, Kozuki T, et al. Phase I study to evaluate the safety and tolerability of MEDI4736, an anti-programmed cell death ligand1 (PD-L1) antibody, in Japanese patients with advanced solid tumors [abstract no. 3039]. J Clin Oncol. 2015;33(Suppl):3039.Google Scholar
  29. 29.
    Karzai F, Madan RA, Owens H, et al. Combination of PDL-1 and PARP inhibition in an unselected population with metastatic castrate-resistant prostate cancer (mCRPC) [abstract no. 5026 plus poster]. J Clin Oncol. 2017;35(Suppl):5026.Google Scholar
  30. 30.
    Lee JM, Santos Zimmer AD, Lipkowitz S, et al. Phase I study of the PD-L1 inhibitor, durvalumab (MEDI4736; D) in combination with a PARP inhibitor, olaparib (O) or a VEGFR inhibitor, cediranib (C) in women’s cancers (NCT02484404) [abstract no. 3015]. J Clin Oncol. 2016;34(Suppl):3015.Google Scholar
  31. 31.
    Slomovitz BM, Moore KM, Youssoufian H, et al. A phase I/II study of durvalumab alone or in combination with AXAL in recurrent/persistent or metastatic cervical or human papillomavirus (HPV) + squamous cell cancer of the head and neck (SCCHN): preliminary phase I results [abstract no. P241]. J Immunother Cancer. 2016;4(Suppl 1):134.Google Scholar
  32. 32.
    Ribas A, Butler M, Lutzky J, et al. Phase I study combining anti-PD-L1 (MEDI4736) with BRAF (dabrafenib) and/or MEK (trametinib) inhibitors in advanced melanoma [abstract no. 3003]. J Clin Oncol. 2015;33(Suppl):3003.Google Scholar
  33. 33.
    Takahashi Y, Fujikawa K, Sagawa T, et al. A phase 1 study to assess the safety and tolerability of tremelimumab alone and in combination with MEDI4736 in Japanese patients with advanced solid malignancies [abstract no. 512]. Eur J Cancer. 2015;51(Suppl 3):S107.CrossRefGoogle Scholar
  34. 34.
    Hong D, Falchook G, Cook CE, et al. A phase 1b study (SCORES) assessing safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of durvalumab combined with AZD9150 or AZD5069 in patients with advanced solid malignancies and SCCHN [abstract no. 1049PD]. Ann Oncol. 2016;27(Suppl 6). doi:10.1093/annonc/mdw378.04.
  35. 35.
    Levy A, Massard C, Soria JC, et al. Concurrent irradiation with the anti-programmed cell death ligand-1 immune checkpoint blocker durvalumab: single centre subset analysis from a phase 1/2 trial. Eur J Cancer. 2016;68:156–62.CrossRefPubMedGoogle Scholar
  36. 36.
    Roche. Roche receives FDA approval for complementary PD-L1 (SP263) biomarker test in urothelial carcinoma [media release]. 2 May 2017. http://www.roche.com.
  37. 37.
    AstraZeneca. Clinical trials appendix: Q1 2017 results update. 2017. https://www.astrazeneca.com. Accessed 29 May 2017.

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

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