Aim: To analyze the late-stage failures of monoclonal antibody drugs. The later a drug fails in development, the more time and expense is incurred by the sponsor. Methods: We review the late stage, Phase III, failures of 21 monoclonal antibody drugs between 2014 and 2019 using published and publicly available information to characterize the reasons for these failures. Results: In some cases, the failures are unavoidable due to the lack of adequate science, but in others, we characterize the causes of such failures and recommend how such failures may have been avoided. Conclusion: By learning from previous mistakes and adhering to the principles and recommendations provided, it is possible to avoid these common pitfalls, increasing the likelihood of success in phase III clinical trials, and thus securing regulatory approval.

Keywords:
Late-stage failure, Lampalizumab, Bococizumab, Tabalumab, Solanezumab, Bavituximab, Sirukumab
1.
PhRMA. Modernizing drug discovery, development & approval. 2016 Mar 31. [last accessed January 20, 2018]. Available from: http://www.phrma.org/report/policy-solutions-modernizing-drug-discovery-development-and-approval.
2.
Pharmaceutical Technology. Counting the cost of failure in drug development. 2017 June 19. [last accessed January 20, 2018]. Available from: https://www.pharmaceutical-technology.com/features/featurecounting-the-cost-of-failure-in-drug-development-5813046/.
3.
Amplion. Fail early, fail fast – and increase likelihood-of-approval. 2017 Feb 14. [last accessed January 24, 2018]. Available from: http://www.amplion.com/biomarker-trends/fail-early-fail-fast-increase-likelihood-of-approval.
4.
Seeking Alpha. Big pharma’s mantra: fail early, fail fast. 2010 July 7. [last accessed January 24, 2018]. Available from: https://seekingalpha.com/article/213440-big-pharmas-mantra-fail-early-fail-fast.
5.
Hwang TJ, Carpenter D, Lauffenburger JC, Wang B, Franklin JM, Kesselheim AS. Failure of investigational drugs in late-stage clinical development and publication of trial tesults. JAMA Intern Med. 2016 Dec;176(12):1826–33.
6.
Parasrampuria DA, Benet LZ, Sharma A. Why drugs fail in late stages of development: case study analyses from the last decade and recommendations. AAPS J. 2018 Mar;20(3):46.
7.
Paul J. Reducing the risk of late-stage failures. [last accessed March 5, 2018]. Available from: https://pharma.elsevier.com/pharma-rd/reducing-the-risk-of-late-phase-failures/.
8.
Merck and Pfizer’s Phase III lung cancer trial of avelumab fails. [last accessed March 5, 2018]. Available from: https://www.drugdevelopment-technology.com/news/merck-pfizers-phase-iii-lung-cancer-trial-avelumab-fails/.
9.
Seattle Genetics discontinues Phase 3 CASCADE trial of vadastuximab talarine (SGN-CD33A) in frontline acute myeloid lymphoma. [last accessed March 5, 2018]. Available from: https://www.businesswire.com/news/home/20170619005466/en/Seattle-Genetics-Discontinues-Phase-3-CASCADE-Trial.
10.
Morrow T, Felcone LH. Defining the difference: what makes biologics unique. Biotechnol Healthc. 2004 Sep;1(4):24–9.
11.
BioWorld. Biologics’ share of medicine chest grows, and so do the pricing concerns. [last accessed January 24, 2018]. Available from: http://www.bioworld.com/content/biologics-share-medicine-chest-grows-and-so-do-pricing-concerns.
12.
U.S. News & World Report. Biologics: the drugs transforming medicine. 2017 July 25. [last accessed January 24, 2018]. Available from: https://www.usnews.com/news/healthcare-of-tomorrow/articles/2017-07-25/biologics-the-drugs-that-are-transforming-medicine.
13.
Rhoades W, Dickson D, Do DV. Potential role of lampalizumab for treatment of geographic atrophy. Clin Ophthalmol. 2015 Jun;9:1049–56.
14.
Holz FG, Sadda SR, Busbee B, Chew EY, Mitchell P, Tufail A, et al.; Chroma and Spectri Study Investigators. Efficacy and safety of lampalizumab for geographic atrophy due to age-related macular degeneration: Chroma and Spectri Phase 3 Randomized Clinical Trials. JAMA Ophthalmol. 2018 Jun;136(6):666–77.
15.
Wang R, Lagakos SW, Ware JH, Hunter DJ, Drazen JM. Statistics in medicine—reporting of subgroup analyses in clinical trials. N Engl J Med. 2007 Nov;357(21):2189–94.
16.
Burke JF, Sussman JB, Kent DM, Hayward RA. Three simple rules to ensure reasonably credible subgroup analyses. BMJ. 2015 Nov;351:h5651.
17.
Rhoades W, Dickson D, Do DV. Potential role of lampalizumab for treatment of geographic atrophy [Retraction]. Clin Ophthalmol. 2015 Jun;9:1135.
18.
Spigel DR, Ervin TJ, Ramlau RA, Daniel DB, Goldschmidt JH Jr, Blumenschein GR Jr, et al. Randomized phase II trial of Onartuzumab in combination with erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2013 Nov;31(32):4105–14.
19.
Iveson T, Donehower RC, Davidenko I, Tjulandin S, Deptala A, Harrison M, et al. Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study. Lancet Oncol. 2014 Aug;15(9):1007–18.
20.
Spigel DR, Edelman MJ, O’Byrne K, Paz-Ares L, Mocci S, Phan S, et al. Results From the Phase III Randomized Trial of Onartuzumab Plus Erlotinib Versus Erlotinib in Previously Treated Stage IIIB or IV Non-Small-Cell Lung Cancer: METLung. J Clin Oncol. 2017 Feb;35(4):412–20.
21.
Shah MA, Bang YJ, Lordick F, Alsina M, Chen M, Hack SP, et al. Effect of fluorouracil, leucovorin, and oxaliplatin with or without onartuzumab in HER2-negative, MET-positive gastroesophageal adenocarcinoma: the METGastric randomized clinical trial. JAMA Oncol. 2017 May;3(5):620–7.
22.
Catenacci DV, Tebbutt NC, Davidenko I, Murad AM, Al-Batran SE, Ilson DH, et al. Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1467–82.
23.
Ridker PM, Revkin J, Amarenco P, Brunell R, Curto M, Civeira F, et al.; SPIRE Cardiovascular Outcome Investigators. Cardiovascular efficacy and safety of bococizumab in high-risk patients. N Engl J Med. 2017 Apr;376(16):1527–39.
24.
Ballantyne CM, Neutel J, Cropp A, Duggan W, Wang EQ, Plowchalk D, et al. Results of bococizumab, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9, from a randomized, placebo-controlled, dose-ranging study in statin-treated subjects with hypercholesterolemia. Am J Cardiol. 2015 May;115(9):1212–21.
25.
Ridker PM, Tardif JC, Amarenco P, Duggan W, Glynn RJ, Jukema JW, et al.; SPIRE Investigators. Lipid-reduction variability and antidrug-antibody formation with bococizumab. N Engl J Med. 2017 Apr;376(16):1517–26.
26.
Pfizer discontinues global development of bococizumab, its investigational PCSK9 inhibitor. 2016 Nov 1. Available from: https://www.pfizer.com/news/press-release/press-release-detail/pfizer_discontinues_global_development_of_bococizumab_its_investigational_pcsk9_inhibitor.
27.
Pfizer abandons cholesterol drug bococizumab, writes it off as an earnings loss. 2016 Nov 3. Available from: https://www.biospace.com/article/pfizer-abandons-cholesterol-drug-bococizumab-writes-it-off-as-an-earnings-loss-/.
28.
Pfizer ends development of its PCSK9 inhibitor. 2016 Nov 1. Available from: http://www.cardiobrief.org/2016/11/01/pfizers-ends-development-of-its-pcsk9-inhibitor/.
29.
Harding FA, Stickler MM, Razo J, DuBridge RB. The immunogenicity of humanized and fully human antibodies: residual immunogenicity resides in the CDR regions. MAbs. 2010 May-Jun;2(3):256–65.
30.
Sheiner LB. Learning versus confirming in clinical drug development. Clin Pharmacol Ther. 1997 Mar;61(3):275–91.
31.
Panettieri RA Jr, Sjöbring U, Péterffy A, Wessman P, Bowen K, Piper E, et al. Tralokinumab for severe, uncontrolled asthma (STRATOS 1 and STRATOS 2): two randomised, double-blind, placebo-controlled, phase 3 clinical trials. Lancet Respir Med. 2018 Jul;6(7):511–25.
32.
Isenberg DA, Petri M, Kalunian K, Tanaka Y, Urowitz MB, Hoffman RW, et al. Efficacy and safety of subcutaneous tabalumab in patients with systemic lupus erythematosus: results from ILLUMINATE-1, a 52-week, phase III, multicentre, randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 2016 Feb;75(2):323–31.
33.
Merrill JT, van Vollenhoven RF, Buyon JP, Furie RA, Stohl W, Morgan-Cox M, et al. Efficacy and safety of subcutaneous tabalumab, a monoclonal antibody to B-cell activating factor, in patients with systemic lupus erythematosus: results from ILLUMINATE-2, a 52-week, phase III, multicentre, randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 2016 Feb;75(2):332–40.
34.
Schiff M, Combe B, Dörner T, Kremer JM, Huizinga TW, Veenhuizen M, et al. Efficacy and safety of tabalumab, an anti-BAFF monoclonal antibody, in patients with moderate-to-severe rheumatoid arthritis and inadequate response to TNF inhibitors: results of a randomised, double-blind, placebo-controlled, phase 3 study. RMD Open. 2015 Aug;1(1):e000037.
35.
Smolen JS, Weinblatt ME, van der Heijde D, Rigby WF, van Vollenhoven R, Bingham CO 3rd, et al. Efficacy and safety of tabalumab, an anti-B-cell-activating factor monoclonal antibody, in patients with rheumatoid arthritis who had an inadequate response to methotrexate therapy: results from a phase III multicentre, randomised, double-blind study. Ann Rheum Dis. 2015 Aug;74(8):1567–70.
36.
Lilly discontinues phase 3 rheumatoid arthritis program for tabalumab based on efficacy results. 2013 Feb 7. Available from: https://investor.lilly.com/news-releases/news-release-details/lilly-discontinues-phase-3-rheumatoid-arthritis-program.
37.
Lilly to discontinue development of tabalumab based on efficacy results in phase 3 lupus studies. 2014 Oct 2. Available from: https://investor.lilly.com/news-releases/news-release-details/lilly-discontinue-development-tabalumab-based-efficacy-results.
38.
Witcher J, Fleischmann R, Chindalore VL, Hansen RJ, Hu L, Radtke D, et al. Pharmacokinetics and safety of single doses of tabalumab in subjects with rheumatoid arthritis or systemic lupus erythematosus. Br J Clin Pharmacol. 2016 May;81(5):908–17.
39.
Genovese MC, Bojin S, Biagini IM, Mociran E, Cristei D, Mirea G, et al. Tabalumab in rheumatoid arthritis patients with an inadequate response to methotrexate and naive to biologic therapy: a phase II, randomized, placebo-controlled trial. Arthritis Rheum. 2013 Apr;65(4):880–9.
40.
Genovese MC, Fleischmann RM, Greenwald M, Satterwhite J, Veenhuizen M, Xie L, et al. Tabalumab, an anti-BAFF monoclonal antibody, in patients with active rheumatoid arthritis with an inadequate response to TNF inhibitors. Ann Rheum Dis. 2013 Sep;72(9):1461–8.
41.
Genovese MC, Lee E, Satterwhite J, Veenhuizen M, Disch D, Berclaz PY, et al. A phase 2 dose-ranging study of subcutaneous tabalumab for the treatment of patients with active rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis. 2013 Sep;72(9):1453–60.
42.
Greenwald M, Szczepanski L, Kennedy A, Veenhuizen M, Komocsar WJ, Polasek E, et al. A 52-week, open-label study evaluating the safety and efficacy of tabalumab, an anti-B-cell-activating factor monoclonal antibody, for rheumatoid arthritis. Arthritis Res Ther. 2014 Aug;16(4):415.
43.
Mujtaba MA, Komocsar WJ, Nantz E, Samaniego MD, Henson SL, Hague JA, et al. Effect of Treatment With Tabalumab, a B Cell-Activating Factor Inhibitor, on Highly Sensitized Patients With End-Stage Renal Disease Awaiting Transplantation. Am J Transplant. 2016 Apr;16(4):1266–75.
44.
GSK announces regulatory submissions for subcutaneous formulation of Benlysta® (belimumab) for patients with systemic lupus disease. 2016 Sep 23. Available from: https://us.gsk.com/en-us/media/press-releases/2016/gsk-announces-regulatory-submissions-for-subcutaneous-formulation-of-benlysta-belimumab-for-patients-with-systemic-lupus-disease/.
45.
Cummings JL, Morstorf T, Zhong K. Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimers Res Ther. 2014 Jul;6(4):37.
46.
DeMattos RB, Bales KR, Cummins DJ, Dodart JC, Paul SM, Holtzman DM. Peripheral anti-A β antibody alters CNS and plasma A β clearance and decreases brain A β burden in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA. 2001 Jul;98(15):8850–5.
47.
Elder GA, Gama Sosa MA, De Gasperi R. Transgenic mouse models of Alzheimer’s disease. Mt Sinai J Med. 2010 Jan-Feb;77(1):69–81.
48.
Siemers ER, Friedrich S, Dean RA, Gonzales CR, Farlow MR, Paul SM, et al. Safety and changes in plasma and cerebrospinal fluid amyloid β after a single administration of an amyloid β monoclonal antibody in subjects with Alzheimer disease. Clin Neuropharmacol. 2010 Mar-Apr;33(2):67–73.
49.
Farlow M, Arnold SE, van Dyck CH, Aisen PS, Snider BJ, Porsteinsson AP, et al. Safety and biomarker effects of solanezumab in patients with Alzheimer’s disease. Alzheimers Dement. 2012 Jul;8(4):261–71.
50.
Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, et al.; Alzheimer’s Disease Cooperative Study Steering Committee; Solanezumab Study Group. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014 Jan;370(4):311–21.
51.
Honig LS, Vellas B, Woodward M, Boada M, Bullock R, Borrie M, et al. Trial of solanezumab for mild dementia due to Alzheimer’s Disease. N Engl J Med. 2018 Jan;378(4):321–30.
52.
Siemers ER, Sundell KL, Carlson C, Case M, Sethuraman G, Liu-Seifert H, et al. Phase 3 solanezumab trials: secondary outcomes in mild Alzheimer’s disease patients. Alzheimers Dement. 2016 Feb;12(2):110–20.
53.
Ioannidis JP. Extrapolating from Animals to Humans. Sci Transl Med. 2012 Sep;4(151):151ps15.
54.
Has Alzheimer’s research been wrong for 20 years? 2017 May 15. Available from: https://www.alzheimers.net/2014-04-07/beta-amyloid-wrong-protein/.
55.
Is the leading theory about Alzheimer’s wrong? 2017 Feb 22. Available from: https://www.theatlantic.com/health/archive/2017/02/alzheimers-amyloid-hypothesis/517185/.
56.
There’s new evidence that the dominant approach to Alzheimer’s may be completely wrong. 2018 Aug 13. Available from: https://www.marketwatch.com/story/theres-new-evidence-that-the-dominant-approach-to-alzheimers-may-be-completely-wrong-2018-08-09.
57.
Corren J, Lemanske RF Jr, Hanania NA, Korenblat PE, Parsey MV, Arron JR, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011 Sep;365(12):1088–98.
58.
Hanania NA, Korenblat P, Chapman KR, Bateman ED, Kopecky P, Paggiaro P, et al. Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials. Lancet Respir Med. 2016 Oct;4(10):781–96.
59.
Wenzel S, Castro M, Corren J, Maspero J, Wang L, Zhang B, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016 Jul;388(10039):31–44.
60.
Castro M, Corren J, Pavord ID, Maspero J, Wenzel S, Rabe KF, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018 Jun;378(26):2486–96.
61.
FDA approves asthma indication for Dupixent® (dupilumab). 2018 Oct 19. [last accessed February 24, 2019]. Available from: https://newsroom.regeneron.com/news-releases/news-release-details/fda-approves-asthma-indication-dupixentr-dupilumab.
62.
Gerber DE, Horn L, Boyer M, Sanborn R, Natale R, Palmero R, et al. Randomized phase III study of docetaxel plus bavituximab in previously treated advanced non-squamous non-small-cell lung cancer. Ann Oncol. 2018 Jul;29(7):1548–53.
63.
Gerber DE, Spigel DR, Giorgadze D, Shtivelband M, Ponomarova OV, Shan JS, et al. Docetaxel combined with bavituximab in previously treated, advanced nonsquamous non-small-cell lung cancer. Clin Lung Cancer. 2016 May;17(3):169–76.
64.
Peregrine Pharmaceuticals, Inc. Corporate Fact Sheet. 2014 Jan. [last accessed December 4, 2018]. Available from: http://files.shareholder.com/downloads/PPHM/0x0x621302/6cfcdcd0-7d2d-4395-89cb-0d33fc4a8c85/jan_corp_fact_sheet.pdf.
65.
Laforest R, Dehdashti F, Liu Y, Frye J, Frye S, Luehmann H, et al. First-in-man evaluation of 124I-PGN650: A PET tracer for detecting phosphatidylserine as a biomarker of the solid tumor microenvironment. Mol Imaging. 2017 Jan-Dec;16:1536012117733349.
66.
Williams S. Just how important is bavituximab to Peregrine Pharmaceuticals? 2014 Mar 11. [last accessed December 4, 2018]. Available from: https://www.fool.com/investing/general/2014/03/11/just-how-important-is-bavituximab-to-peregrine-pha.aspx.
67.
Feuerstein A. Peregrine Pharma stock craters on lung cancer drug blowup. 2012 Sep 24 (last accessed December 4, 2018). https://www.thestreet.com/story/11716746/1/peregrine-pharma-stock-crater-on-lung-cancer-drug-blowup.html.
68.
Avid offloads phase III mAb, becomes pure play CDMO. 2018 Feb 20 (last accessed December 4, 2018). https://www.biopharma-reporter.com/Article/2018/02/20/Avid-offloads-Phase-III-mAb-becomes-pureplay-CDMO.
69.
Peregrine Pharmaceuticals announces name change to Avid Bioservices as part of transition to dedicated contract development and manufacturing organization (CDMO). 2018 Jan 5. [last accessed December 4, 2018]. Available from: http://ir.avidbio.com/news-releases/news-release-details/peregrine-pharmaceuticals-announces-name-change-avid-bioservices?ReleaseID=1053451.
70.
Takeuchi T, Thorne C, Karpouzas G, Sheng S, Xu W, Rao R, et al. Sirukumab for rheumatoid arthritis: the phase III SIRROUND-D study. Ann Rheum Dis. 2017 Dec;76(12):2001–8.
71.
Aletaha D, Bingham CO 3rd, Tanaka Y, Agarwal P, Kurrasch R, Tak PP, et al. Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory to anti-TNF therapy (SIRROUND-T): a randomised, double-blind, placebo-controlled, parallel-group, multinational, phase 3 study. Lancet. 2017 Mar;389(10075):1206–17.
72.
Taylor PC, Schiff MH, Wang Q, Jiang Y, Zhuang Y, Kurrasch R, et al. Efficacy and safety of monotherapy with sirukumab compared with adalimumab monotherapy in biologic-naïve patients with active rheumatoid arthritis (SIRROUND-H): a randomised, double-blind, parallel-group, multinational, 52-week, phase 3 study. Ann Rheum Dis. 2018 May;77(5):658–66.
73.
Janssen submits application seeking approval of sirukumab in United States for rheumatoid arthritis. 2016 Sep 23. [last accessed December 5, 2018]. Available from: https://www.jnj.com/media-center/press-releases/janssen-submits-application-seeking-approval-of-sirukumab-in-united-states-for-rheumatoid-arthritis.
74.
Worcester S. FDA committee rejects sirukumab approval on safety concerns. 2017 Aug 2. [last accessed December 5, 2018]. Available from: https://www.mdedge.com/rheumatologynews/article/143848/rheumatoid-arthritis/fda-committee-rejects-sirukumab-approval-safety.
75.
FDA Arthritis Advisory Committee (AAC) FDA Introductory Remarks, BLA 761057: Sirukumab for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or are intolerant to one or more disease modifying anti-rheumatic drugs (DMARDs). 2017 Aug 2. [last accessed December 6, 2018]. Available from: https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM570356.pdf.
76.
Janssen receives complete response letter from U.S. FDA for sirukumab biologics license application. 2017 Sep 22. [last accessed December 5, 2018]. Available from: https://www.jnj.com/media-center/press-releases/janssen-receives-complete-response-letter-from-us-fda-for-sirukumab-biologics-license-application.
77.
J&J halts sirukumab development, talacotuzumab trial. 2017 Oct 17. [last accessed December 5, 2018]. Available from: https://www.genengnews.com/topics/translational-medicine/jj-halts-sirukumab-development-talacotuzumab-trial/.
78.
FDA Guidance for Industry, Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products. 1998 May. [last accessed December 9, 2018]. Available from: https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm072008.pdf.
79.
Sirukumab presentation to the Arthritis Advisory Committee, Janssen R&D, LLC. 2017 Aug 2. [last accessed December 8, 2018]. Available from: https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM570357.pdf.
80.
Summary minutes of the Arthritis Advisory Committee Meeting. 2017 Aug 2. [last accessed December 9, 2018]. Available from: https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM575678.pdf.
81.
FDA Briefing Document, Arthritis Advisory Committee Meeting. 2017 Aug 2. [last accessed December 8, 2018]. Available from: https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM569150.pdf.
82.
Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016 Oct;388(10055):2023–38.
83.
Ma X, Xu S. TNF inhibitor therapy for rheumatoid arthritis. Biomed Rep. 2013 Mar;1(2):177–84.
84.
Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016 Jan;68(1):1–26.
85.
AstraZeneca provides update on the phase III MYSTIC trial of Imfinzi and tremelimumab in stage IV non-small cell lung cancer. 2018 Nov 16. [last accessed February 24, 2019]. Available from: https://www.astrazeneca.com/media-centre/press-releases/2018/astrazeneca-provides-update-on-the-phase-iii-mystic-trial-of-imfinzi-and-tremelimumab-in-stage-iv-non-small-cell-lung-cancer16112018.html.
86.
Taylor NP. AstraZeneca’s tremelimumab fails another phase 3 cancer trial. 2018 Dec 7. [last accessed February 24, 2019]. Available from: https://www.fiercebiotech.com/biotech/astrazeneca-s-tremelimumab-fails-another-phase-3-cancer-trial.
87.
Ribas A, Kefford R, Marshall MA, Punt CJ, Haanen JB, Marmol M, et al. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J Clin Oncol. 2013 Feb;31(5):616–22.
88.
Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010 Aug;363(8):711–23.
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