Durvalumab

{{Short description|Pharmaceutical drug}} {{Use dmy dates|date=November 2025}} {{cs1 config |name-list-style=vanc |display-authors=6}} {{Infobox drug | type = mab | image = Durvalumab PD-L1 5X8M.pdb.png | alt = | caption = Antigen-binding fragment of durvalumab (pale green) in complex with PD-L1 (pink). {{PDB|5X8M}}.

| mab_type = mab | source = u | target = CD274

| pronounce = | tradename = Imfinzi | Drugs.com = {{drugs.com|monograph|durvalumab}} | MedlinePlus = a617030 | DailyMedID = Durvalumab | pregnancy_AU = D | pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Durvalumab (Imfinzi) Use During Pregnancy | website=Drugs.com | date=30 August 2019 | url=https://www.drugs.com/pregnancy/durvalumab.html | access-date=7 February 2020 | archive-date=29 August 2021 | archive-url=https://web.archive.org/web/20210829124022/https://www.drugs.com/pregnancy/durvalumab.html | url-status=live }}</ref><ref>[https://www.tga.gov.au/resources/auspar/auspar-imfinzi AusPAR: Imfinzi]</ref><ref>[https://www.tga.gov.au/resources/auspar/auspar-durvalumab AusPAR: Durvalumab]</ref> | pregnancy_category = | routes_of_administration = Intravenous | class = | ATC_prefix = L01 | ATC_suffix = FF03 | ATC_supplemental = | biosimilars =

| legal_AU = S4 | legal_AU_comment = <ref>{{cite web | title=Imfinzi (AstraZeneca Pty Ltd) | website=Therapeutic Goods Administration (TGA) | date=5 December 2022 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/imfinzi-astrazeneca-pty-ltd-2 | access-date=9 April 2023 | archive-date=18 March 2023 | archive-url=https://web.archive.org/web/20230318050444/https://www.tga.gov.au/resources/prescription-medicines-registrations/imfinzi-astrazeneca-pty-ltd-2 | url-status=live }}</ref><ref>{{cite web|url=https://www.tga.gov.au/resources/auspar/auspar-imfinzi |title=Auspar: Imfinzi |date=8 December 2023|access-date=18 June 2024}}</ref><ref>[https://www.tga.gov.au/resources/prescription-medicines-registrations/imfinzi-astrazeneca-pty-ltd-5 Australia IMFINZI (AstraZeneca Pty Ltd)]</ref> | legal_BR =  | legal_BR_comment = | legal_CA = Rx-only | legal_CA_comment = /{{nbsp}}Schedule D<ref>{{cite web | url=https://dhpp.hpfb-dgpsa.ca/review-documents/resource/RDS00366 | title=Regulatory Decision Summary - Imfinzi | publisher=Health Canada | date=23 October 2014 | access-date=6 September 2022 | archive-date=7 June 2022 | archive-url=https://web.archive.org/web/20220607073415/https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?lang=en&linkID=RDS00366 | url-status=live }}</ref><ref>{{cite web | title=Cancer therapies | website=Health Canada | date=8 May 2018 | url=https://www.canada.ca/en/services/health/drug-health-products/drug-medical-device-highlights-2017/approved-drugs/cancer-therapies.html | access-date=13 April 2024}}</ref> | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK = POM | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Imfinzi FDA label" /> | legal_EU = Rx-only | legal_EU_comment = <ref name="Imfinzi EPAR">{{cite web | title=Imfinzi EPAR | website=European Medicines Agency (EMA) | date=30 October 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/imfinzi | access-date=30 September 2020 | archive-date=28 August 2021 | archive-url=https://web.archive.org/web/20210828065950/https://www.ema.europa.eu/en/medicines/human/EPAR/imfinzi | url-status=live }}</ref> | legal_UN =  | legal_UN_comment = | legal_status =

| C=6502 | H=10018 | N=1742 | O=2024 | S=42 }}

'''Durvalumab''',<ref>{{cite journal | vauthors = ((World Health Organization)) | year = 2015 | title = International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 74 | journal = WHO Drug Information | volume = 29 | issue = 3 | hdl = 10665/331070 | hdl-access = free | author-link = World Health Organization }}</ref> sold under the brand name '''Imfinzi''', is an anti-cancer medication used for treatment of various types of cancer.<ref name="Imfinzi FDA label" /> It was developed by Medimmune/AstraZeneca.<ref name="FDA 20170506">{{Cite web|url=https://www.fda.gov/drugs/resources-information-approved-drugs/durvalumab-imfinzi |title=Durvalumab (Imfinzi) |website=U.S. Food and Drug Administration (FDA) |access-date=6 May 2017|archive-date=8 May 2017|archive-url=https://web.archive.org/web/20170508150028/https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm555930.htm|url-status=dead}}</ref> It is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that binds to programmed cell death ligand 1 (PD-L1) on cancer cells and blocks interactions with PD-1 and CD80 (B7.1) on T cells.<ref name="Imfinzi FDA label" />

Durvalumab is an immune checkpoint inhibitor drug.<ref name=":0">{{cite journal | vauthors = Syn NL, Teng MW, Mok TS, Soo RA | title = De-novo and acquired resistance to immune checkpoint targeting | journal = The Lancet. Oncology | volume = 18 | issue = 12 | pages = e731–e741 | date = December 2017 | pmid = 29208439 | doi = 10.1016/s1470-2045(17)30607-1 }}</ref> It was approved in for medical use in the United States in May 2017,<ref name="Imfinzi FDA label" /><ref name="FDA 20170506" /><ref>{{cite web | title=FDA approves durvalumab for extensive-stage small cell lung cancer | website=U.S. Food and Drug Administration (FDA) | date=27 March 2020 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-extensive-stage-small-cell-lung-cancer | archive-url=https://web.archive.org/web/20200804145011/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-extensive-stage-small-cell-lung-cancer | url-status=dead | archive-date=4 August 2020 | access-date=19 July 2024}}</ref><ref>{{cite journal | vauthors = Mathieu L, Shah S, Pai-Scherf L, Larkins E, Vallejo J, Li X, Rodriguez L, Mishra-Kalyani P, Goldberg KB, Kluetz PG, Theoret MR, Beaver JA, Pazdur R, Singh H | title = FDA Approval Summary: Atezolizumab and Durvalumab in Combination with Platinum-Based Chemotherapy in Extensive Stage Small Cell Lung Cancer | journal = The Oncologist | volume = 26 | issue = 5 | pages = 433–438 | date = May 2021 | pmid = 33687763 | pmc = 8100557 | doi = 10.1002/onco.13752 }}</ref> and in the European Union in September 2018.<ref name="Imfinzi EPAR" />

== Medical uses == The US Food and Drug Administration (FDA) approved durvalumab for certain types of bladder, lung, and biliary tract cancer:<ref name="Imfinzi FDA label">{{cite web | title=Imfinzi- durvalumab injection, solution | website=DailyMed | date=5 June 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8baba4ea-2855-42fa-9bd9-5a7548d4cec3 | access-date=30 September 2020 | archive-date=28 August 2021 | archive-url=https://web.archive.org/web/20210828070027/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8baba4ea-2855-42fa-9bd9-5a7548d4cec3 | url-status=live }}</ref><ref name="FDA PR 20220902">{{cite web | title=FDA approves durvalumab | website=U.S. Food and Drug Administration | date=2 September 2022 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-locally-advanced-or-metastatic-biliary-tract-cancer | access-date=5 September 2022 | archive-date=6 September 2022 | archive-url=https://web.archive.org/web/20220906053710/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-locally-advanced-or-metastatic-biliary-tract-cancer | url-status=dead }} {{PD-notice}}</ref><ref>{{cite press release | title=Imfinzi (durvalumab) plus chemotherapy approved in the US as the first immunotherapy regimen for patients with advanced biliary tract cancer | website=AstraZeneca | date=5 September 2022 | url=https://www.astrazeneca-us.com/media/press-releases/2022/imfinzi-durvalumab-plus-chemotherapy-approved-in-the-us-as-the-first-immunotherapy-regimen-for-patients-with-advanced-biliary-tract-cancer-09052022.html | access-date=19 July 2024}}</ref> * Adults with locally advanced or metastatic urothelial carcinoma who either have disease progression during or following platinum-containing chemotherapy or have disease progression within twelve months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. * Adults with unresectable, Stage III non-small cell lung cancer whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. * In combination with etoposide and either carboplatin or cisplatin, as first-line treatment for adults with extensive-stage small cell lung cancer. * In combination with gemcitabine and cisplatin for adults with locally advanced or metastatic biliary tract cancer (BTC).<ref name="FDA PR 20220902" />

In June 2024, the US FDA approved durvalumab with carboplatin plus paclitaxel, followed by single-agent durvalumab, for adults with primary advanced or recurrent endometrial cancer that is mismatch repair deficient.<ref name="FDA 20240614">{{cite web | title=FDA approves durvalumab with chemotherapy for mismatch repair deficient primary advanced or recurrent endometrial cancer | website=U.S. Food and Drug Administration (FDA) | date=14 June 2024 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-chemotherapy-mismatch-repair-deficient-primary-advanced-or-recurrent | access-date=18 June 2024}} {{PD-notice}}</ref><ref>{{cite press release |date=17 June 2024 |title=Imfinzi (durvalumab) plus chemotherapy approved in the US for mismatch repair deficient advanced or recurrent endometrial cancer |url=https://www.astrazeneca-us.com/media/press-releases/2024/imfinzi-durvalumab-plus-chemotherapy-approved-in-the-us-for-mismatch-repair-deficient-advanced-or-recurrent-endometrial-cancer.html |website=AstraZeneca }}</ref>

In August 2024, the FDA approved durvalumab with platinum-containing chemotherapy as neoadjuvant treatment, followed by single-agent durvalumab as adjuvant treatment after surgery for adults with resectable (tumors ≥ 4 cm and/or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.<ref name="FDA 20240815">{{cite web | title=FDA approves neoadjuvant/adjuvant durvalumab for resectable non-small cell lung cancer | website=U.S. Food and Drug Administration | date=15 August 2024 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvantadjuvant-durvalumab-resectable-non-small-cell-lung-cancer | archive-url=https://web.archive.org/web/20240815214920/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvantadjuvant-durvalumab-resectable-non-small-cell-lung-cancer | url-status=dead | archive-date=15 August 2024 | access-date=16 August 2024}} {{PD-notice}}</ref> Efficacy was evaluated in AEGEAN (NCT03800134), a randomized, double-blind, placebo-controlled multicenter trial in 802 participants with previously untreated and resectable squamous or non-squamous NSCLC (stage IIA to select stage IIIB [AJCC, 8th edition]).<ref name="FDA 20240815" /><ref name="auto">{{Cite web |title=A Study of Neoadjuvant/adjuvant Durvalumab for the Treatment of Patients with Resectable Non-small Cell Lung Cancer - AEGEAN |url=https://clinicaltrials.gov/study/NCT03800134 |access-date=20 August 2024 |website=clinicaltrials.gov}}</ref> Participants were randomized (1:1) to either durvalumab or placebo, with platinum-based chemotherapy, every 3 weeks for up to 4 cycles (neoadjuvant treatment) followed by either continued single-agent durvalumab or placebo, every 4 weeks for up to 12 cycles (adjuvant treatment).<ref name="FDA 20240815" />

In December 2024, the FDA expanded the indication of durvalumab to include adults with limited-stage small cell lung cancer whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.<ref name="FDA Imfinzi 20241204">{{cite web | title=FDA approves durvalumab for limited-stage small cell lung cancer | website=U.S. Food and Drug Administration (FDA) | date=4 December 2024 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-limited-stage-small-cell-lung-cancer | archive-url=https://web.archive.org/web/20241204230754/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-limited-stage-small-cell-lung-cancer | url-status=dead | archive-date=4 December 2024 | access-date=5 December 2024}} {{PD-notice}}</ref> The efficacy was evaluated in ADRIATIC (NCT03703297), a randomized, double-blind, placebo-controlled trial in 730 participants with LS-SCLC whose disease had not progressed following concurrent platinum-based chemotherapy and radiation therapy.<ref name="FDA Imfinzi 20241204" /> Participants were randomized 1:1:1 to receive durvalumab as a single agent, durvalumab in combination with tremelimumab, or placebo.<ref name="FDA Imfinzi 20241204" />

In March 2025, the FDA approved durvalumab with gemcitabine and cisplatin as neoadjuvant treatment, followed by single agent durvalumab as adjuvant treatment following radical cystectomy, for adults with muscle invasive bladder cancer.<ref name="FDA Imfinzi 20250328">{{cite web | title=FDA approves durvalumab for muscle invasive bladder cancer | website=U.S. Food and Drug Administration | date=28 March 2025 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-muscle-invasive-bladder-cancer | archive-url=https://web.archive.org/web/20250516222014/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-muscle-invasive-bladder-cancer | url-status=dead | archive-date=16 May 2025 | access-date=29 March 2025}} {{PD-notice}}</ref> The efficacy was evaluated in NIAGARA (NCT03732677), a randomized, open-label, multicenter, phase III trial enrolling 1,063 participants who were candidates for radical cystectomy and had not received prior systemic therapy for bladder cancer.<ref name="FDA Imfinzi 20250328" /> Participants were randomized (1:1) to receive neoadjuvant durvalumab with chemotherapy followed by adjuvant durvalumab after surgery or neoadjuvant chemotherapy followed by surgery alone.<ref name="FDA Imfinzi 20250328" />

In November 2025, the US FDA approved durvalumab with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT chemotherapy) as neoadjuvant and adjuvant treatment, followed by single agent durvalumab, for adults with resectable gastric or gastroesophageal junction adenocarcinoma.<ref>{{cite web | title=FDA approves durvalumab for resectable gastric or gastroesophageal junction adenocarcinoma | website=U.S. Food and Drug Administration | date=25 November 2025 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-resectable-gastric-or-gastroesophageal-junction-adenocarcinoma | access-date=26 November 2025}} {{PD-notice}}</ref>

== History == === Clinical trials === thumb|Immunotherapy: mechanism of action for Durvalumab, Pembrolizumab, Ipilimumab, Atezolizumab.<ref name="pmid33171686">{{cite journal | vauthors = Nasser NJ, Gorenberg M, Agbarya A | title = First line Immunotherapy for Non-Small Cell Lung Cancer | journal = Pharmaceuticals | location = Basel, Switzerland | volume = 13 | issue = 11 | date = November 2020 | page = 373 | pmid = 33171686 | pmc = 7695295 | doi = 10.3390/ph13110373 | doi-access = free }}</ref> A phase Ib clinical trial of durvalumab and tremelimumab showed some activity in non-small cell lung cancer (NSCLC)<ref>{{cite journal | vauthors = Ribrag V, Lee ST, Rizzieri D, Dyer MJ, Fayad L, Kurzrock R, Andritsos L, Bouabdallah R, Hayat A, Bacon L, Jiang Y, Miah K, Delafont B, Hamid O, Anyanwu S, Martinez P, Hess B | title = A Phase 1b Study to Evaluate the Safety and Efficacy of Durvalumab in Combination With Tremelimumab or Danvatirsen in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma | journal = Clinical Lymphoma, Myeloma & Leukemia | volume = 21 | issue = 5 | pages = 309–317.e3 | date = May 2021 | pmid = 33632668 | doi = 10.1016/j.clml.2020.12.012 }}</ref> Phase I data in advanced metastatic urothelial bladder (Study 1108) has led to FDA breakthrough therapy designation.<ref name=":0" /><ref>{{cite web|url=http://www.streetinsider.com/Corporate+News/AstraZenecas+(AZN)+Durvalumab+Granted+FDA+Breakthrough+Therapy+Designation/11329642.html |title=AstraZeneca's (AZN) Durvalumab Granted FDA Breakthrough Therapy Designation |archive-url=https://web.archive.org/web/20210828070013/https://www.streetinsider.com/Corporate+News/AstraZenecas+%28AZN%29+Durvalumab+Granted+FDA+Breakthrough+Therapy+Designation/11329642.html |archive-date=28 August 2021 |website=StreeInsider.com |date=17 February 2016}}</ref> Early results of a phase I trial combining durvalumab and gefitinib in participants with lung cancer "showed promise".<ref>{{cite web|url=https://www.mesotheliomahelp.org/2016/05/clinical-trial-points-promising-drug-combo-lung-cancer-mesothelioma-patients-42357/|title=Promising Drug for Lung Cancer and Mesothelioma Patients|date=19 May 2016|access-date=27 May 2016|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828070022/https://www.mesotheliomahelp.org/treatment/clinical-trials/promising-drug-lung-cancer-mesothelioma/|url-status=live}}</ref> A phase I clinical trial is currently underway using durvalumab with a TLR 7/8 agonist (MEDI 9197) for solid tumors.<ref>{{ClinicalTrialsGov|NCT02556463|A Study of MEDI9197 in Subjects With Solid Tumors or CTCL and in Combination With Durvalumab and/or Palliative Radiation in Subjects With Solid Tumors}}</ref> A phase 1b/2a trial is underway combining durvalumab with an HPV DNA vaccine (MEDI 0457) in participants with HPV-associated recurrent/metastatic head and neck cancer.<ref>{{ClinicalTrialsGov|NCT03162224?|Safety and Efficacy of MEDI0457 and Durvalumab in Patients With HPV Associated Recurrent/Metastatic Head and Neck Cancer}}</ref>

==== MYSTIC ==== In July 2017, AstraZeneca announced that a phase III trial of durvalumab with tremelimumab as a first-line treatment of non-small cell lung cancer failed to meet its primary endpoint of progression-free survival.<ref>{{cite web|url=https://www.astrazeneca.com/media-centre/press-releases/2017/astrazeneca-reports-initial-results-from-the-ongoing-mystic-trial-in-stage-iv-lung-cancer-27072017.html|title=AstraZeneca reports initial results from the ongoing MYSTIC trial in Stage IV lung cancer|website=www.astrazeneca.com|date=27 July 2017 |access-date=23 August 2017|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828065958/https://www.astrazeneca.com/media-centre/press-releases/2017/astrazeneca-reports-initial-results-from-the-ongoing-mystic-trial-in-stage-iv-lung-cancer-27072017.html|url-status=live}}</ref>

==== PACIFIC ==== In November 2017, the double-blinded phase III AstraZeneca PACIFIC clinical trial demonstrated the efficacy of durvalumab in the treatment of stage III non-small cell lung cancer.<ref>{{cite web|url=https://www.astrazeneca.com/media-centre/press-releases/2017/astrazeneca-presents-superior-progression-free-survival-for-imfinzi-in-the-pacific-trial-of-patients-with-locally-advanced-unresectable-lung-cancer-at-esmo-2017-congress-08092017.html|title=AstraZeneca presents superior progression-free survival for Imfinzi in the PACIFIC trial of patients with locally-advanced unresectable lung cancer at ESMO 2017 Congress|date=Sep 2017|website=www.astrazeneca.com|access-date=9 December 2017|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828070035/https://www.astrazeneca.com/media-centre/press-releases/2017/astrazeneca-presents-superior-progression-free-survival-for-imfinzi-in-the-pacific-trial-of-patients-with-locally-advanced-unresectable-lung-cancer-at-esmo-2017-congress-08092017.html|url-status=live}}</ref> 709 participants with stage III NSCLC who did not have disease progression after two or more cycles of a platinum-based chemotherapy were randomly assigned to receive durvalumab or a placebo as consolidation therapy for their lung cancer. Durvalumab increased the median progression-free survival from 5.6 months (placebo) to 16.8 months (durvalumab); the 12 month progression-free survival rate was increased from 35.3% (placebo) to 55.9% (durvalumab), and the 18 month progression-free survival rate was increased from 27.0% (placebo) to 44.2% (durvalumab).<ref name=":0" /> The median time to death or distant metastases was also increased from 14.6 months (placebo) to 23.2 months (durvalumab). Extreme side effects were also increased from 26.1% of participants (placebo) to 29.9% of participants (durvalumab).<ref>{{cite journal | vauthors = Fitzpatrick O, Naidoo J | title = Immunotherapy for Stage III NSCLC: Durvalumab and Beyond | journal = Lung Cancer: Targets and Therapy| volume = 12 | pages = 123–131 | date = 2 November 2021 | pmid = 34754256 | pmc = 8572112 | doi = 10.2147/LCTT.S305466 | doi-access = free }}</ref>

==== CASPIAN ==== In March 2021, the open-label, sponsor-blind (AstraZeneca), randomised, controlled phase III trial at 209 cancer treatment centres in 23 countries worldwide (CASPIAN) demonstrated the efficacy of durvalumab in combination with platinum-based chemotherapy in the treatment of small cell lung cancer.<ref>{{Cite web|url = https://clinicaltrials.gov/ct2/show/results/NCT03043872|title = A Phase III, Randomized, Multicenter, Open-Label, Comparative Study to Determine the Efficacy of Durvalumab or Durvalumab and Tremelimumab in Combination with Platinum-Based Chemotherapy for the First-Line Treatment in Patients with Extensive Disease Small-Cell Lung Cancer (SCLC) (CASPIAN)|date = 30 September 2021|journal = |access-date = 6 September 2022|archive-date = 3 June 2021|archive-url = https://web.archive.org/web/20210603224813/https://clinicaltrials.gov/ct2/show/results/NCT03043872|url-status = live}}</ref>

Between March 2017, and May 2018, 972 participants were screened and 805 were randomly assigned (268 to durvalumab plus tremelimumab plus platinum–etoposide, 268 to durvalumab plus platinum–etoposide, and 269 to platinum–etoposide). As of 27 January 2020, the median follow-up was 25·1 months (IQR 22·3–27·9). Durvalumab plus tremelimumab plus platinum–etoposide was not associated with a significant improvement in overall survival versus platinum–etoposide (hazard ratio [HR] 0·82 [95% CI 0·68–1·00]; p=0·045); median overall survival was 10·4 months (95% CI 9·6–12·0) versus 10·5 months (9·3–11·2). Durvalumab plus platinum–etoposide showed sustained improvement in overall survival versus platinum–etoposide (HR 0·75 [95% CI 0·62–0·91]; nominal p=0·0032); median overall survival was 12·9 months (95% CI 11·3–14·7) versus 10·5 months (9·3–11·2). The most common any-cause grade 3 or worse adverse events were neutropenia (85 [32%] of 266 participants in the durvalumab plus tremelimumab plus platinum–etoposide group, 64 [24%] of 265 participants in the durvalumab plus platinum–etoposide group, and 88 [33%] of 266 participants in the platinum–etoposide group) and anaemia (34 [13%], 24 [9%], and 48 [18%]). Any-cause serious adverse events were reported in 121 (45%) participants in the durvalumab plus tremelimumab plus platinum–etoposide group, 85 (32%) in the durvalumab plus platinum–etoposide group, and 97 (36%) in the platinum–etoposide group. Treatment-related deaths occurred in 12 (5%) participants in the durvalumab plus tremelimumab plus platinum–etoposide group (death, febrile neutropenia, and pulmonary embolism [n=2 each]; enterocolitis, general physical health deterioration and multiple organ dysfunction syndrome, pneumonia, pneumonitis and hepatitis, respiratory failure, and sudden death [n=1 each]), six (2%) participants in the durvalumab plus platinum–etoposide group (cardiac arrest, dehydration, hepatotoxicity, interstitial lung disease, pancytopenia, and sepsis [n=1 each]), and two (1%) in the platinum–etoposide group (pancytopenia and thrombocytopenia [n=1 each]).<ref>{{cite journal | vauthors = Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Każarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L | title = Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial | journal = The Lancet. Oncology | volume = 22 | issue = 1 | pages = 51–65 | date = January 2021 | pmid = 33285097 | doi = 10.1016/S1470-2045(20)30539-8 | s2cid = 227948919 | url = https://cris.maastrichtuniversity.nl/en/publications/699cc4ed-41d7-496b-aa00-08d146318f16 }}</ref>

==== TOPAZ-1 ==== Efficacy was evaluated in TOPAZ-1 (NCT03875235), a randomized, double-blind, placebo-controlled, multiregional trial that enrolled 685 participants with histologically confirmed locally advanced unresectable or metastatic BTC who had not previously received systemic therapy for advanced disease.<ref name="FDA PR 20220902" />

Trial demographics were as follows: 56% Asian, 37% White, 2% Black, and 4% other race; 7% Hispanic or Latino; 50% male and 50% female; median age was 64 years (range 20-85) and 47% were 65 years or older.<ref name="FDA PR 20220902" /> Fifty-six percent had intrahepatic cholangiocarcinoma, 25% had gallbladder cancer, and 19% had extrahepatic cholangiocarcinoma.<ref name="FDA PR 20220902" />

The major efficacy outcome measure was overall survival (OS).<ref name="FDA PR 20220902" /> Tumor assessments were conducted every 6 weeks for the first 24 weeks, then every 8 weeks until confirmed objective disease progression.<ref name="FDA PR 20220902" /> A statistically significant improvement in OS was demonstrated in participants randomized to receive durvalumab with gemcitabine and cisplatin compared to those randomized to receive placebo with gemcitabine and cisplatin.<ref name="FDA PR 20220902" /> Median OS was 12.8 months (95% CI: 11.1, 14) and 11.5 months (95% CI: 10.1, 12.5) in the durvalumab and placebo arms, respectively (hazard ratio 0.80; 95% CI: 0.66, 0.97, p=0.021).<ref name="FDA PR 20220902" /> The median progression-free survival was 7.2 months (95% CI: 6.7, 7.4) and 5.7 months (95% CI: 5.6, 6.7) in the durvalumab and placebo arms, respectively. Investigator-assessed overall response rate was 27% (95% CI: 22% - 32%) and 19% (95% CI: 15%-23%) in the durvalumab and placebo arms, respectively.<ref name="FDA PR 20220902" />

==== DUO-E ==== Efficacy was evaluated in DUO-E (NCT04269200), a randomized, multicenter, double-blind, placebo-controlled trial in participants with primary advanced or recurrent endometrial cancer.<ref name="FDA 20240614" /> Participants were randomized (1:1:1) to one of the following treatment arms: durvalumab 1,120 mg with carboplatin plus paclitaxel every three weeks for a maximum of six cycles.<ref name="FDA 20240614" /> Following completion of chemotherapy, participants received durvalumab 1,500 mg every four weeks as maintenance until disease progression;<ref name="FDA 20240614" /> placebo with carboplatin and paclitaxel every three weeks for a maximum of six cycles<ref name="FDA 20240614" /> Following completion of chemotherapy, participants received placebo every four weeks until disease progression;<ref name="FDA 20240614" /> an additional investigational combination regimen.<ref name="FDA 20240614" /><ref name=":1">{{cite journal | vauthors = Westin SN, Moore K, Chon HS, Lee JY, Thomes Pepin J, Sundborg M, Shai A, de la Garza J, Nishio S, Gold MA, Wang K, McIntyre K, Tillmanns TD, Blank SV, Liu JH, McCollum M, Contreras Mejia F, Nishikawa T, Pennington K, Novak Z, De Melo AC, Sehouli J, Klasa-Mazurkiewicz D, Papadimitriou C, Gil-Martin M, Brasiuniene B, Donnelly C, Del Rosario PM, Liu X, Van Nieuwenhuysen E | title = Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial | journal = Journal of Clinical Oncology | volume = 42 | issue = 3 | pages = 283–299 | date = January 2024 | pmid = 37864337 | pmc = 10824389 | doi = 10.1200/JCO.23.02132 }}</ref><ref name=":2">{{Cite report |url=https://clinicaltrials.gov/study/NCT04269200 |title=A Randomised, Multicentre, Double-blind, Placebo-controlled, Phase III Study of First-line Carboplatin and Paclitaxel in Combination With Durvalumab, Followed by Maintenance Durvalumab With or Without Olaparib in Patients With Newly Diagnosed Advanced or Recurrent Endometrial Cancer (DUO-E) |last=AstraZeneca |date=4 March 2024 |publisher=clinicaltrials.gov |issue=NCT04269200}}</ref>

The most common adverse reactions (>25%) with durvalumab, in combination with carboplatin and paclitaxel, were peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, diarrhea, vomiting, and cough.<ref name="FDA 20240614" />

==== AEGEAN ==== Efficacy was evaluated in AEGEAN (NCT03800134), a randomized, double-blind, placebo-controlled multicenter trial in 802 patients with previously untreated and resectable squamous or non-squamous NSCLC (Stage IIA to select Stage IIIB [AJCC, 8th edition]). Patients were randomized (1:1) to either durvalumab or placebo, with platinum-based chemotherapy, every 3 weeks for up to 4 cycles (neoadjuvant treatment) followed by either continued single-agent durvalumab or placebo, every 4 weeks for up to 12 cycles (adjuvant treatment).<ref name="FDA 20240815" /><ref name="auto"/>

The major efficacy outcome measures were event-free survival (EFS) by blinded independent central review assessment and pathological complete response (pCR) by blinded central pathology review. Median EFS was not reached (95% CI: 31.9, not estimable [NE]) in the durvalumab arm and 25.9 months (95% CI: 18.9, NE) in the placebo arm (hazard ratio 0.68 [95% CI: 0.53, 0.88]; p-value=0.0039). The pCR rate was 17% (95% CI: 13, 21) and 4.3% (95% CI: 2.5, 7) in the durvalumab and placebo arms, respectively. At the time of the prespecified interim analyses, overall survival (OS) was not formally tested for statistical significance; however, a descriptive analysis revealed no clear detriment.<ref name="FDA 20240815" />

The most common adverse reactions (≥20%) were anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash. Of the patients who received neoadjuvant durvalumab, 1.7% were unable to receive surgery due to adverse reactions compared with 1% in the placebo arm.<ref name="FDA 20240815" />

== WHO Confirmation of Falsified IMFINZI == In recent years the awareness of fake drug is on the rise. in December 2024, WHO Alert No. 5/2024 similarly flagged counterfeit IMFINZI in Lebanon, Armenia, and Türkiye, confirmed by AstraZeneca’s lab test.<ref>{{Cite web |title=Medical Product Alert N°5/2024: Falsified IMFINZI (durvalumab) injection 500mg /10ml |url=https://www.who.int/news/item/23-12-2024-medical-product-alert-n-5-2024 |access-date=9 June 2025 |website=www.who.int |language=en}}</ref> In May 2025, the World Health Organization issued Medical Product Alert No. 3/2025: three batches of falsified IMFINZI 500 mg/10 mL were identified in Lebanon, Türkiye, and Iran. All contained no active ingredient, presenting clear harm due to ineffective cancer treatment.<ref>{{Cite web |title=Medical Product Alert N°3/2025: Falsified IMFINZI (durvalumab) injection 500mg/10ml |url=https://www.who.int/news/item/14-05-2025-medical-product-alert-n-3-2025--falsified-imfinzi-(durvalumab)-injection-500mg-10ml |access-date=9 June 2025 |website=www.who.int |language=en}}</ref><ref>{{Cite web |date=14 January 2025 |title=WHO Alert: Counterfeit Cancer Medicines Reported in Europe |url=https://www.safemedicines.org/2025/01/who-alert-counterfeit-cancer-medicines-reported-in-europe.html |access-date=9 June 2025 |website=Partnership for Safe Medicines |language=en-US}}</ref>

The 2025 Counterfeit medication scandal was a major public health and criminal case in Lebanon involving the smuggling, distribution, and administration of counterfeit cancer drugs. The scandal has raised national and international concern after it was revealed that fake medications were substituted for essential chemotherapy treatments, potentially endangering the lives of hundreds of patients.<ref>{{Cite web |title=Judicial Inquiry Underway into Major Counterfeit Cancer Drug Scandal |url=https://en.kataeb.org/articles/judicial-inquiry-underway-into-major-counterfeit-cancer-drug-scandal |access-date=9 June 2025 |website=Lebanese kataeb |language=en}}</ref><ref>{{Cite web |last=Barakat |first=Diana |date=5 June 2025 |title=An international network for smuggling counterfeit cancer drugs has been busted in Lebanon, with several involved individuals, including officers and officials, being arrested. |url=https://www.tesaaworld.com/en/news/international-network-busted-smuggling-counterfeit-cancer-drugs-in-lebanon-arrest-of-involved-individuals-including-officers-and-officials |access-date=9 June 2025 |website=TESAA |language=en}}</ref>

== References == {{reflist}}

{{Targeted cancer therapeutic agents}} {{PD-1_and_PD-L1_inhibitors}} {{Monoclonals for tumors}} {{Monoclonals for immune system}} {{AstraZeneca}} {{Portal bar | Medicine}} {{Authority control}}

Category:Antineoplastic drugs Category:Monoclonal antibodies for tumors Category:Drugs developed by AstraZeneca Category:Orphan drugs