Durvalumab (Imfinzi)

==General information==
Class/mechanism: PD-L1 blocking antibody. PD-L1 (programmed death-1 ligand 1) expressed on tumor cells and tumor-infiltrating immune cells can result in inhibition of anti-tumor immune responses. Durvalumab binds to PD-1 and CD80 (B7.1) receptors on T-cells and antigen presenting cells and prevents PD-L1's inhibitory effects on the immune system. As a result, durvalumab stimulates immune responses, including anti-tumor immune effects. Durvalumab (Imfinzi) package insert Durvalumab (Imfinzi) package insert (locally hosted backup)Imfinzi manufacturer's websiteDurvalumab granted Breakthrough Therapy designation by US FDA for treatment of patients with PD-L1 positive urothelial bladder cancer (AstraZeneca)
Route: IV
Extravasation: no information
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias or the prescribing information.
==Toxicity management==
*Immunotherapy toxicity management
==Diseases for which it is established==
*Cholangiocarcinoma
*Endometrial cancer
*Hepatocellular carcinoma
*Non-small cell lung cancer
*Small cell lung cancer
==Diseases for which it is used==
*Colorectal cancer
*Urothelial carcinoma
==Patient drug information==
*Durvalumab (Imfinzi) package insert
==History of changes in FDA indication==
===Cholangiocarcinoma===
*2022-09-02: Approved in combination with gemcitabine and cisplatin for adult patients with locally advanced or metastatic biliary tract cancer (BTC). (Based on TOPAZ-1)
===Endometrial cancer===
*2024-06-14: Approved with carboplatin plus paclitaxel followed by single-agent durvalumab for adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR). (Based on DUO-E)
===Non-small cell lung cancer===
*2018-02-16: Approved for patients with unresectable stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. (New disease entity; based on PACIFIC)
*2024-08-15: Approved 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. (Based on AEGEAN)
===Small cell lung cancer===
*2020-03-27: Approved in combination with etoposide and either carboplatin or cisplatin as first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). (New disease entity; based on CASPIAN)
*2024-12-04: Approved for adults with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. (Based on ADRIATIC)
===Urothelial carcinoma - WITHDRAWN===
*2017-05-01: Granted accelerated approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy (Initial approval; based on Study 1108)
**2021-02-19: Indication for urothelial carcinoma withdrawn after the confirmatory trial did not meet its primary endpoints. (Based on DANUBE)
*2017-05-01: Granted accelerated approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. (Initial approval; based on Study 1108)
**2021-02-19: Indication for urothelial carcinoma withdrawn after the confirmatory trial did not meet its primary endpoints. (Based on DANUBE)
==History of changes in EMA indication==
===Biliary tract cancers===
*2022-12-16: Extension of indication to include IMFINZI in combination with gemcitabine and cisplatin for the first-line treatment of adults with unresectable or metastatic biliary tract cancer (BTC). (Based on TOPAZ-1)
===Hepatocellular carcinoma===
*2023-01-30: Extension of indication to include IMFINZI in combination with tremelimumab for the first line treatment of adults with advanced or unresectable hepatocellular carcinoma (uHCC). (Based on HIMALAYA)
*2023-10-12: CHMP adopted new indication Imfinzi as monotherapy is indicated for the first line treatment of adults with advanced or unresectable hepatocellular carcinoma (HCC).
===Non-small cell lung cancer===
*2018-09-21: Initial authorization as Imfinzi. Imfinzi as monotherapy is indicated for the treatment of locally advanced, unresectable non-small cell lung cancer (NSCLC) in adults whose tumours express PD-L1 on at least 1% of tumour cells and whose disease has not progressed following platinum-based chemoradiation therapy. (Based on PACIFIC)
*2023-01-30: Extension of indication to include first-line treatment, with Imfinzi in combination with tremelimumab and platinum-based chemotherapy, of adults with metastatic NSCLC with no sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) positive mutations. (Based on POSEIDON)
===Small cell lung cancer===
*2020-08-27: Extension of Indication to include the use of IMFINZI in combination with etoposide and either carboplatin or cisplatin for the first-line treatment of adults with extensive-stage small cell lung cancer (ES-SCLC). (Based on CASPIAN)
==History of changes in Health Canada indication==
*2017-11-03: Initial notice of compliance with conditions for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum containing chemotherapy.
*2017-11-03: Initial notice of compliance with conditions for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
==History of changes in PMDA indication==
*2018-07-02: Newly indicated for the maintenance treatment of locally-advanced, unresectable non-small cell lung cancer following definitive chemoradiation therapy.
*2020-08-21: New indication and a new dosage for the treatment of extensive-stage small-cell lung cancer.
==Also known as==
*Code name: MEDI-4736
*Brand name: Imfinzi
==References==
Category:Drugs
Category:Intravenous medications
Category:Protein expression-specific medications
Category:Anti-PD-L1 antibodies
Category:Cholangiocarcinoma medications
Category:Colorectal cancer medications
Category:Endometrial cancer medications
Category:Hepatocellular carcinoma medications
Category:Non-small cell lung cancer medications
Category:Small cell lung cancer medications
Category:Urothelial carcinoma medications
Category:FDA approved in 2017
Category:Health Canada approved in 2017
Category:EMA approved in 2018
Category:NMPA approved drugs
Category:PMDA approved in 2018
Category:AstraZeneca product