Database for
Therapeutic Antibodies
Therapeutic Antibodies
| Entry ID | 102 |
| INN | Durvalumab |
| Status | Approved |
| Drug code(s) | MEDI-4736 |
| Brand name | IMFINZI |
| mAb sequence source | mAb human |
| General Molecular Category | Naked monospecific |
| Format, general category | Full length Ab |
| Format details | None |
| Isotype (Fc) | IgG1 |
| Light chain isotype | kappa |
| Linker | None |
| Ave. DAR | None |
| Conjugated/fused moiety | None |
| Discovery method/technology | Transgenic mouse (Xenomouse) |
| Target(s) | PD-L1 |
| Indications of clinical studies | Bladder cancer, Head & neck cancer, Non-small cell lung cancer; Solid tumors (advanced malignant melanoma, renal cell carcinoma, non-small cell lung cancer, or colorectal cancer) |
| Primary therapeutic area | Cancer |
| Most advanced stage of development (global) | Approved EU, US, Japan, Australia, Canada |
| Status | Active |
| Start of clinical phase (IND filing or first Phase 1) | August 15, 2012 |
| Start of Phase 2 | March 15, 2014 |
| Start of Phase 3 | June 01, 2014 |
| Date BLA/NDA submitted to FDA | October 13, 2016 |
| Year of first approval (global) | 2017 |
| Date of first US approval | May 01, 2017 |
| INN, US product name | Durvalumab |
| US or EU approved indications | Unresectable stage 3 non-small cell lung cancer that has not progressed after concurrent platinum-based chemotherapy and radiation therapy; in combination with etoposide and either carboplatin or cisplatin, as first-line treatment of adult patients with extensive-stage small cell lung cancer; treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC) in combination with chemotherapy (gemcitabine plus cisplatin). |
| Company | AstraZeneca |
| Licensee/Partner | Celgene |
| Comments about company or candidate | Feb 2021: AstraZeneca announced the voluntary withdrawal of the Imfinzi (durvalumab) indication in the US for previously treated adult patients with locally advanced or metastatic bladder cancer. This decision was made in consultation with the Food and Drug Administration (FDA). Approved May 1, 2017 in US; approved Sep 25, 2018 in EU Rolling BLA initiated in Sep 2016; priority review. Breakthrough therapy designation for bladder cancer, NSCLC; FT designation for head and neck cancer. NCT02125461 Phase 3 study in NSCLC started in June 2014. NCT02027961 started in Nov 2013 listed as Phase 1 as well as Phase 1/2; NCT02087423 Phase 2 study started in March 2014. US IND filed in June 2012 |
| Full address of company | Cambridge, United Kingdom Europe United Kingdom https://www.astrazeneca.com/our-company/contact-us.html |
Immune checkpoint target. Ab generation: IgG2 and IgG4 XenoMouse animals were immunized with human PD-L1-Ig or CHO cells expressing human PD-L1. Hybridomas were established, and supernatants screened for binding to human PD-L1–transfected HEK 293 cells and inhibition of PD-1 binding to PD-L1 expressing CHO cells. MEDI4736 was selected based on a favorable affinity, activity, and specificity profile in these screens. The constant domain of the antibody was then exchanged for a human IgG1 triple-mutant domain (L234F; L235E; P331S). This constant domain contains three point mutations that reduce binding to C1q and the Fc gamma receptors, resulting in reduced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity
| Anticipated events | None |
| Factor(s) contributing to discontinuation | None |