Avelumab

Avelumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetPD-L1
Names
Trade namesBavencio
Other namesMSB0010718C
Clinical data
Drug classprogrammed death-ligand 1 (PD-L1) blocker[1]
Main usesMerkel cell carcinoma, urothelial carcinoma, renal cell cancer[2]
Side effectsTiredness, nausea, diarrhea, infusion reaction, weight loss[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
    Routes of
    use    		Intravenous infusion
    Typical dose800 mg[2]
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa617006
    Legal
    License data
    Legal status
    • AU: S4 (Prescription only)
    • US: ℞-only [2]
    • EU: Rx-only
    Pharmacokinetics
    MetabolismProteolysis
    Elimination half-life6.1 days
    Chemical and physical data
    FormulaC6374H9898N1694O2010S44
    Molar mass143831.79 g·mol−1

    Avelumab, sold under the brand name Bavencio, is a medication used to treat Merkel cell carcinoma, urothelial carcinoma, and renal cell cancer.[2] It is used as long as it is working and the side effects are not too severe.[1] It is give by injection into a vein.[2]

    Common side effects include tiredness, nausea, diarrhea, infusion reaction, and weight loss.[1] Other side effects may include immune-mediated disorders such as pneumonitis and colitis, as well as low red blood cells and shortness of breath.[2][1] Use in pregnancy may harm the baby.[3] It is a monoclonal antibody that attaches to the protein programmed death-ligand 1 (PD-L1), allowing the immune system to kill cancer cells.[1]

    Avelumab was approved for medical use in the United States and Europe in 2017.[2][1] In the United Kingdom a 4 weeks costs the NHS about £6,100 as of 2021.[4] In the United States this amount costs about 14,300 USD.[5]

    Medical uses

    In March 2017, the US Food and Drug Administration (FDA) granted accelerated approval to avelumab for the treatment of adults and children twelve years and older with metastatic Merkel-cell carcinoma (MCC).[6][7]

    In May 2017, the FDA approved avelumab for people with locally advanced or metastatic urothelial carcinoma whose disease progressed during or following platinum-containing chemotherapy or within twelve months of neoadjuvant or adjuvant platinum-containing chemotherapy.[8]

    In May 2019, the FDA approved avelumab in combination with axitinib for the first-line treatment of people with advanced renal cell carcinoma.[9]

    In June 2020, the FDA approved avelumab for the maintenance treatment of people with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.[10]

    Dosage

    It is given at a dose of 800 mg every two weeks.[2]

    Contraindications

    No contraindications have been specified.[11]

    Side effects

    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.[11][12]

    The most common serious risks are immune-mediated, where the body’s immune system attacks healthy cells or organs, such as the lungs (pneumonitis), liver (hepatitis), colon (colitis), hormone-producing glands (endocrinopathies) and kidneys (nephritis).[7] In addition, there is a risk of serious infusion-related reactions.[7] Patients who experience severe or life-threatening infusion-related reactions should stop using avelumab.[7] Women who are pregnant or breastfeeding should not take avelumab because it may cause harm to a developing fetus or a newborn baby.[7]

    Interactions

    As avelumab is an antibody, no pharmacokinetic interactions with other drugs are expected.[12]

    Pharmacology

    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.[13] Therefore, avelumab belongs to the group of immune checkpoint blockade cancer therapies.

    History

    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 in Phase III.[14]

    In May 2017, avelumab was approved in the United States for the treatment of adults and children twelve years and older with metastatic Merkel cell carcinoma (MCC), including those who have not received prior chemotherapy.[7] This is the first FDA-approved treatment for metastatic MCC, a rare, aggressive form of skin cancer.[7]

    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.[15]

    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.[15]

    The approval of avelumab was based on data from a single-arm trial of 88 patients with metastatic MCC who had been previously treated with at least one prior chemotherapy regimen.[7] The trial measured the percentage of patients who experienced complete or partial shrinkage of their tumors (overall response rate) and, for patients with a response, the length of time the tumor was controlled (duration of response).[7] Of the 88 patients who received Bavencio in the trial, 33 percent experienced complete or partial shrinkage of their tumors.[7] The response lasted for more than six months in 86 percent of responding patients and more than 12 months in 45 percent of responding patients.[7]

    The US Food and Drug Administration (FDA) granted the application for avelumab priority review, breakthrough therapy, and orphan drug designations.[7]

    The FDA granted accelerated approval of Bavencio to EMD Serono Inc.[7]

    In June 2020, avelumab was approved by the US Food and Drug Administration (FDA) for the indication of the maintenance treatment for people with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.[16]

    Efficacy of avelumab for maintenance treatment of urothelial carcinoma was investigated in the JAVELIN Bladder 100 trial (NCT02603432), a randomized, multi-center, open-label trial that enrolled 700 patients with unresectable, locally advanced or metastatic urothelial carcinoma that had not progressed with four to six cycles of first-line platinum-containing chemotherapy.[16] Patients were randomized (1:1) to receive either avelumab intravenously every 2 weeks plus best supportive care (BSC) or BSC alone.[16] Treatment was initiated within 4-10 weeks after last chemotherapy dose.[16]

    References

    1. 1 2 3 4 5 6 7 "Bavencio". Archived from the original on 25 May 2021. Retrieved 16 January 2022.
    2. 1 2 3 4 5 6 7 8 "Bavencio- avelumab injection, solution, concentrate". DailyMed. 2 July 2020. Archived from the original on 3 August 2020. Retrieved 2 August 2020.
    3. 1 2 "Avelumab (Bavencio) Use During Pregnancy". Drugs.com. 29 May 2019. Archived from the original on 27 September 2020. Retrieved 2 August 2020.
    4. ↑ BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 908. ISBN 978-0857114105.
    5. ↑ "Bavencio Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 23 April 2021. Retrieved 16 January 2022.
    6. ↑ "Pfizer, Merck KGaA fourth to market with PD-1/L1 inhibitor". Archived from the original on 9 October 2021. Retrieved 24 January 2021.
    7. 1 2 3 4 5 6 7 8 9 10 11 12 13 "FDA approves first treatment for rare form of skin cancer". U.S. Food and Drug Administration (FDA) (Press release). 23 March 2017. Archived from the original on 1 July 2020. Retrieved 2 August 2020. Public Domain This article incorporates text from this source, which is in the public domain.
    8. ↑ "FDA grants accelerated approval to avelumab for urothelial carcinoma". U.S. Food and Drug Administration. 9 May 2017. Archived from the original on 26 November 2020. Retrieved 30 September 2020. Public Domain This article incorporates text from this source, which is in the public domain.
    9. ↑ "FDA approves avelumab plus axitinib for renal cell carcinoma". U.S. Food and Drug Administration (FDA). 14 May 2019. Archived from the original on 1 September 2020. Retrieved 29 September 2020.
    10. ↑ "FDA approves avelumab for urothelial carcinoma maintenance treatment". U.S. Food and Drug Administration (FDA). 30 June 2020. Archived from the original on 21 October 2020. Retrieved 29 September 2020.
    11. 1 2 "Bavencio Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists, Inc. 27 January 2020. Archived from the original on 1 August 2017. Retrieved 2 August 2020.
    12. 1 2 "Bavencio: EPAR - Product Information" (PDF). European Medicines Agency. 18 September 2017. Archived (PDF) from the original on 17 June 2018. Retrieved 24 January 2021.
    13. ↑ Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, et al. (July 2013). "Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma". The New England Journal of Medicine. 369 (2): 134–44. doi:10.1056/NEJMoa1305133. PMC 4126516. PMID 23724846.
    14. ↑ Merck-Pfizer Alliance. "Merck-Pfizer Alliance Avelumab Fact Sheet" (PDF). Archived from the original (PDF) on 17 May 2017. Retrieved 2 December 2015.
    15. 1 2 Kaufman HL, Russell JS, Hamid O, Bhatia S, Terheyden P, D'Angelo SP, et al. (January 2018). "Updated efficacy of avelumab in patients with previously treated metastatic Merkel cell carcinoma after ≥1 year of follow-up: JAVELIN Merkel 200, a phase 2 clinical trial". Journal for Immunotherapy of Cancer. 6 (1): 7. doi:10.1186/s40425-017-0310-x. PMC 5774167. PMID 29347993.
    16. 1 2 3 4 "FDA approves avelumab for urothelial carcinoma maintenance treatment". U.S. Food and Drug Administration (FDA). 30 June 2020. Archived from the original on 21 October 2020. Retrieved 2 August 2020. Public Domain This article incorporates text from this source, which is in the public domain.
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