Atezolizumab
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Humanized |
| Target | PD-L1 |
| Clinical data | |
| Trade names | Tecentriq |
| AHFS/Drugs.com | tecentriq |
| Legal status | |
| Legal status |
|
| Identifiers | |
| Synonyms | MPDL3280A |
| CAS Number | 1380723-44-3 |
| DrugBank | DB11595 |
| ChemSpider | none |
| UNII | 52CMI0WC3Y |
| Chemical and physical data | |
| Formula | C6446H9902N1706O1998S42 |
| Molar mass | 144,612.59 g·mol−1 |
Atezolizumab (trade name Tecentriq) is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1). It is currently in clinical trials as an immunotherapy for several types of solid tumors.[1] It is under investigation by Genentech/Roche.
In April 2016 Roche announced that atezolizumab had been granted fast track status for lung cancer by the FDA.[2]
In May 2016 it was approved by the FDA for bladder cancer treatment.[3]
Medical uses
In May 2016 FDA granted accelerated approval to atezolizumab for locally advanced or metastatic urothelial carcinoma treatment after failure of chemo- or radiotherapy.[3] In October 2016, FDA approved atezolizumab for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose disease progressed during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving atezolizumab.[4]
Adverse effects
The most common adverse effects in studies were fatigue, decreased appetite, nausea, and infections. Urinary tract infection was the most common severe adverse effect.[5]
Pharmacology
Mechanism of action
Atezolizumab blocks the interaction of PD-L1 with programmed cell death protein 1 (PD-1) and CD80 (B7-1). PD-L1 can be highly expressed on certain tumors, which is thought to lead to reduced activation of immune cells (cytotoxic T-cells in particular) that might otherwise recognize and attack the cancer. Inhibition of PD-L1 by atezolizumab can remove this inhibitor effect and thereby engender an anti-tumor response. It is one of several ways to block inhibitory signals related to T-cell activation, a more general strategy known as "immune checkpoint inhibition."
For some cancers (notably bladder) the probability of benefit is related to PD-L1 expression, but most cancers with PD-L1 expression still do not respond, and many (about 15%) without PD-L1 expression do respond.
Research
As of 2016, it is currently in clinical trials for colorectal cancer, melanoma, breast cancer, non-small-cell lung carcinoma, bladder cancer, renal cell carcinoma.[6][7]
Promising results have been observed for melanoma and non-small-cell lung cancer, and bladder cancer.[1]
A phase 1 trial reported a 19% objective response rate in metastatic triple-negative breast cancer.[8]
References
- 1 2 "Genentech Presents Positive Results of Atezolizumab in Advanced Bladder Cancer". Oct 2, 2015.
- ↑ Shields, Michael (11 Apr 2016). "Roche says FDA fast tracks atezolizumab in specific type of lung cancer". Reuters. Retrieved 11 Apr 2016.
- 1 2 "FDA approves new, targeted treatment for bladder cancer". FDA. 18 May 2016. Retrieved 20 May 2016.
- ↑ "FDA approves new treatment for non-small cell lung cancer". FDA. 18 Oct 2016. Retrieved 18 May 2016.
- ↑ FDA Professional Drug Information for Tecentriq.
- ↑ "Search of: MPDL3280A - List Results - ClinicalTrials.gov".
- ↑ Bendell, Johanna C.; Kim, Tae Won; Goh, Boon C.; Wallin, Jeffrey; Oh, Do-Youn; Han, Sae-Won; Lee, Carrie B.; Hellmann, Matthew David; Desai, Jayesh; Lewin, Jeremy Howard; Solomon, Benjamin J.; Chow, Laura Quan Man; Miller, Wilson H.; Gainor, Justin F.; Flaherty, Keith; Infante, Jeffrey R.; Das-Thakur, Meghna; Foster, Paul; Cha, Edward; Bang, Yung-Jue. "Clinical activity and safety of cobimetinib (cobi) and atezolizumab in colorectal cancer (CRC). - 2016 ASCO Annual Meeting Abstracts". Meeting Abstracts.
- ↑ "MPDL3280A Shows Activity in Triple-Negative Breast Cancer".