|Elimination half-life||6.1 days|
Avelumab (trade name Bavencio) is a fully human monoclonal antibody developed by Merck KGaA and Pfizer as a pharmaceutical drug for use in immunotherapy, originally for the treatment of non-small-cell lung carcinoma (NSCLC).
Avelumab targets the protein programmed death-ligand 1 (PD-L1). It has received orphan drug designation by the European Medicines Agency (EMA) for the treatment of gastric cancer in January 2017. The US Food and Drug Administration (FDA) approved it in March 2017 for Merkel-cell carcinoma, an aggressive type of skin cancer. The EMA approved it in September 2017 for the same indication.
Approval was based on data from an open-label, single-arm, multi-center clinical trial (JAVELIN Merkel 200 trial). All patients had histologically confirmed metastatic MCC with disease progression on or after chemotherapy administered for metastatic disease.
ORR was assessed by an independent review committee according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The overall response rate (ORR) was 33% (95% confidence interval [CI]: 23.3, 43.8), with 11% complete and 22% partial response rates. Among the 29 responding patients, the response duration ranged from 2.8 to 23.3+ months with 86% of responses durable for 6 months or longer. Responses were observed in patients regardless of PD-L1 tumor expression or presence of Merkel cell polyomavirus.
No contraindications have been specified.
Safety data were evaluated in 1738 patients. The most common serious adverse reactions to avelumab are immune-mediated adverse reactions (pneumonitis, hepatitis, colitis, adrenal insufficiency, hypo- and hyperthyroidism, diabetes mellitus, and nephritis) and life-threatening infusion reactions. Among the 88 patients enrolled in the JAVELIN Merkel 200 trial, the most common adverse reactions were fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, rash, decreased appetite, and peripheral edema. Serious adverse reactions that occurred in more than one patient in the trial were acute kidney injury, anemia, abdominal pain, ileus, asthenia, and cellulitis.
Mechanism of action
Avelumab is a whole monoclonal antibody of isotype IgG1 that binds to the programmed death-ligand 1 (PD-L1) and therefore inhibits binding to its receptor programmed cell death 1 (PD-1). Formation of a PD-1/PD-L1 receptor/ligand complex leads to inhibition of CD8+ T cells, and therefore inhibition of an immune reaction. Immunotherapy aims at ceasing this immune blockage by blocking those receptor ligand pairs. In the case of avelumab, the formation of PD-1/PDL1 ligand pairs is blocked and CD8+ T cell immune response should be increased. PD-1 itself has also been a target for immunotherapy. Therefore, avelumab belongs to the group of immune checkpoint blockade cancer therapies.
As of May 2015, according to Merck KGaA and Pfizer, avelumab has been in Phase I clinical trials for bladder cancer, stomach cancer, head and neck cancer, mesothelioma, NSCLC, ovarian cancer and renal cancer. For Merkel-cell carcinoma, Phase II has been reached and for NSCLC there is also a study already in Phase III.
- Merck-Pfizer Alliance. "Merck-Pfizer Alliance Avelumab Fact Sheet" (PDF). Retrieved 2 December 2015.
- "Public summary of opinion on orphan designation: Avelumab for the treatment of gastric cancer" (PDF). European Medicines Agency. 9 January 2017.
- Drugs.com: bavencio.
- "Bavencio: EPAR - Product Information" (PDF). European Medicines Agency. 18 September 2017.
- Pfizer, Merck KGaA fourth to market with PD-1/L1 inhibitor re FDA approves first treatment for rare form of skin cancer. March 2017
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- "Avelumab". Drug Information Portal. U.S. National Library of Medicine.