Avelumab: The Anti-PD-L1 Antibody for Merkel Cell and Urothelial Cancer

Avelumab is an immune checkpoint antibody: a laboratory-made protein, dripped into a vein, that blocks a “brake” molecule cancers use to switch off the immune system’s T cells. In the United States it is approved for Merkel cell carcinoma, an aggressive skin cancer, for urothelial carcinoma (the cancer that most often starts in the lining of the bladder), and, together with the pill axitinib, for advanced kidney cancer. This page explains how the drug works, what the US prescribing information lists it for, what its main trials found, how the label gives it, which side effects the label reports and how often, and what is still not known. The diseases themselves are covered on the Merkel Cell Carcinoma, Bladder Cancer and Renal Cell Carcinoma pages; this page goes deeper into the one drug.

Table of Contents

  1. What Avelumab Is
  2. How Blocking PD-L1 Works
  3. Its Place Among the PD-L1 Antibodies
  4. The Uses on the US Label
  5. JAVELIN Merkel 200 Part A: After Chemotherapy
  6. JAVELIN Merkel 200 Part B: As the First Treatment
  7. JAVELIN Bladder 100: Maintenance After Platinum Chemotherapy
  8. JAVELIN Renal 101: With Axitinib in Kidney Cancer
  9. How the Label Gives the Drug
  10. Immune-Mediated Side Effects and Their Rates on the Label
  11. Infusion Reactions, Heart Events and Other Label Warnings
  12. What Is Not Known
  13. Key Research Papers
  14. Connections
  15. Featured Videos

What Avelumab Is

Avelumab is a monoclonal antibody — a single, precisely copied immune protein grown in cell culture. The US prescribing information describes it as a human immunoglobulin G1 (IgG1) lambda antibody, produced in Chinese hamster ovary cells, with a molecular weight of about 147 kilodaltons. “Human” here means that the protein sequence is fully human rather than partly mouse. The ending -mab in its name marks it as a monoclonal antibody.

The drug comes as a clear, colourless to slightly yellow liquid, 200 mg in 10 mL (20 mg per mL) in a single-dose vial. It is diluted into a bag of salt solution and given as an infusion into a vein in a clinic. It is not a pill.

Avelumab belongs to the wider family of PD-1 and PD-L1 blocking antibodies. Some members of the family block PD-1, the receptor on the T cell; avelumab, like atezolizumab, blocks PD-L1, the partner molecule on the other side. A close relative used in the same Merkel cell cancer, the PD-1 antibody retifanlimab, has its own page: Retifanlimab. The research that led to this family of drugs is covered on the Allison and Honjo page.

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How Blocking PD-L1 Works

T cells are the white blood cells that recognize and kill infected or abnormal cells. Because an unchecked T cell can also damage healthy tissue, the body has “checkpoint” molecules that switch T cells down. One of these is programmed death-ligand 1 (PD-L1). It sits on the surface of other cells and, when it touches the receptor PD-1 on a T cell, tells the T cell to stand down.

The label summarizes the cancer side of this. PD-L1 “may be expressed on tumor cells and tumor-infiltrating immune cells” and can contribute to blocking the immune attack inside a tumor. When PD-L1 binds to PD-1, or to a second receptor called B7.1, it suppresses the killing activity of T cells, their multiplication and their release of signalling proteins. Avelumab attaches to PD-L1 and blocks its contact with both PD-1 and B7.1. The label states that this restores immune responses, including responses against the tumor. In plain words, some cancers survive by pressing the T cells’ off-switch, and avelumab covers the button.

Two further points come from laboratory and animal work, not from patients. The label states that avelumab has also been shown in laboratory tests (in vitro) to trigger antibody-dependent cell-mediated cytotoxicity — a process in which immune cells kill cells that the antibody has coated. And in mice carrying tumors, blocking PD-L1 slowed tumor growth.

The same mechanism explains the side effects. The label describes the whole drug class as “removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions.” Peripheral tolerance is the set of brakes that keeps T cells from attacking the body’s own organs. When it is released, T cells can turn on the lungs, bowel, liver, hormone glands, kidneys, skin and other tissues. Those reactions are described in their own section below.

Merkel cell carcinoma drew early interest for this approach. In the first JAVELIN Merkel 200 report, the authors noted that the cancer is linked both to a virus, Merkel cell polyomavirus, and to ultraviolet-induced mutations, which gave them the rationale for testing a PD-L1/PD-1 antibody. Patients were not selected by PD-L1 level or virus status.

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Its Place Among the PD-L1 Antibodies

Avelumab was not the first PD-L1 antibody to reach patients. A 2017 approval summary written by US Food and Drug Administration (FDA) reviewers records that on May 18, 2016, the agency approved atezolizumab for advanced urothelial carcinoma that had grown during or after platinum chemotherapy, and states that atezolizumab “represents the first approved product directed against PD-L1.” Avelumab’s label gives its own initial US approval as 2017.

What avelumab was first at is a disease. Two long-term reports from the JAVELIN Merkel 200 trial state that in 2017 avelumab became the first approved treatment for patients with metastatic Merkel cell carcinoma.

The road to that approval began with a dose-finding study. In the phase 1a part of the JAVELIN Solid Tumor trial, run at a single US centre, 53 people with advanced solid tumors received avelumab at 1, 3, 10 or 20 mg per kilogram of body weight every 2 weeks between January 2013 and October 2014. Only one dose-limiting side effect occurred, at 20 mg/kg, so a maximum tolerated dose was not reached. Blood tests showed the drug occupying more than 90% of its target at 3 and 10 mg/kg, and a half-life of 95–99 hours (3.9–4.1 days) at the two higher doses. Partial responses occurred in 4 of the 53 (8%), and 30 more (57%) had stable disease. Severe (grade 3–4) treatment-related side effects occurred in 9 people (17%). On the basis of these results the investigators chose 10 mg/kg every 2 weeks for later trials — the dose used in every trial described below.

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The Uses on the US Label

The current US prescribing information, as published on DailyMed (September 2026 version), lists these uses:

The label lists no contraindications, meaning no condition in which the label forbids its use outright; the safety information is carried by the warnings.

For children, the label states that use from age 12 in Merkel cell carcinoma rests on the adult trials, together with drug-level data showing that age and body weight had no clinically meaningful effect on exposure, and on the judgement that the disease runs a similar enough course in adults and older children to extrapolate. Safety and effectiveness below age 12 have not been established.

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JAVELIN Merkel 200 Part A: After Chemotherapy

How it was run. Part A was a single-arm, open-label phase 2 trial — everyone received avelumab, and there was no comparison group. It enrolled 88 adults with stage IV Merkel cell carcinoma that had grown after chemotherapy, at 35 cancer centres in North America, Europe, Australia and Asia, between July 2014 and September 2015. Each received 10 mg/kg every 2 weeks. The main measure was the share of people whose tumors shrank by a set amount (the objective response rate), judged by an independent review committee. People with human immunodeficiency virus (HIV), with weakened immune systems, with blood cancers or with a previous organ transplant were excluded.

First report (2016). After a median follow-up of 10.4 months, tumors shrank in 28 of 88 people (31.8%): 8 complete responses, in which measurable tumor disappeared, and 20 partial responses. Responses were still ongoing in 23 of the 28 (82%). Severe (grade 3) treatment-related side effects occurred in 4 people (5%); there were no grade 4 treatment-related side effects and no treatment-related deaths.

After at least one year (2018). The confirmed response rate was 33.0%, with complete responses in 11.4%. An estimated 74% of responses lasted at least one year. At one year, 30% of people were alive without their cancer growing and 52% were alive. Median overall survival was 12.9 months. The authors reported that responses occurred whether or not the tumor carried the Merkel cell virus, and that response looked more likely in people with fewer earlier treatments, less cancer at the start and PD-L1-positive tumors.

Long-term results (2020 and 2021). With a median follow-up of 40.8 months, the response rate stayed at 33.0%, with complete responses in 10 people (11.4%), and the median duration of response was 40.5 months. Median overall survival was 12.6 months, and 31% were alive at 42 months. Of the long-term survivors (alive beyond 36 months) whose tumors could be tested, 81.8% had PD-L1-positive tumors. After more than 5 years (median follow-up 65.1 months), the 5-year overall survival rate was 26%. It was 28% for PD-L1-positive and 19% for PD-L1-negative tumors; the hazard ratio for that comparison was 0.67, with a 95% confidence interval of 0.36 to 1.25, a range that includes 1, the value meaning no difference.

The current label shows the same Part A figures: 29 of 88 responded (33%), 10 completely (11%), median duration of response 40.5 months, and 66% of responders kept their response for at least 12 months.

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JAVELIN Merkel 200 Part B: As the First Treatment

Part B gave the same dose to people with metastatic Merkel cell carcinoma who had received no earlier drug treatment for their metastatic disease. Again there was no comparison group.

Early look (2018). A preplanned interim analysis looked at 29 people who had been followed for at least 3 months. Tumors shrank in 62.1% of them, and 14 of the 18 responses were still ongoing. No treatment-related deaths or grade 4 side effects occurred. The median age of the first 39 people enrolled was 75 years.

The full group on the label. The early figure came from a small, short-followed group. With all 116 people enrolled, the label reports a response in 46 (40%), complete in 19 (16%), and a median duration of response of 18.2 months; 52% of responders kept their response for at least 12 months. In this group 18% of tumors were PD-L1-positive and 60% carried the Merkel cell virus, and the label states that responses were seen regardless of either.

Four-year follow-up (2024). With a median follow-up of 54.3 months, 72 of the 116 people (62.1%) had died. Median overall survival was 20.3 months, and 38% were alive at 4 years — 48% of those with PD-L1-positive tumors and 35% of those with PD-L1-negative tumors. In total, 48 people (41.4%) went on to other cancer drugs after the study, most often the chemotherapy drugs etoposide and carboplatin. The authors wrote that these results “compared favorably” with historical studies of first-line chemotherapy; no randomized trial in this part compared the two directly.

The pembrolizumab, nivolumab and retifanlimab results in the same cancer are summarized on the Merkel Cell Carcinoma page.

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JAVELIN Bladder 100: Maintenance After Platinum Chemotherapy

The standard first treatment for advanced urothelial carcinoma is platinum-based chemotherapy, but the 2020 trial report notes that its benefit is limited by chemotherapy resistance. JAVELIN Bladder 100 tested whether starting avelumab straight after a successful course of chemotherapy, instead of waiting for the cancer to return, helps people live longer.

How it was run. This phase 3 trial took 700 people with urothelial cancer that could not be removed by surgery or had spread, whose disease had not grown during four to six cycles of gemcitabine with cisplatin or carboplatin. They were assigned at random to best supportive care alone or best supportive care plus avelumab (350 in each group). The label describes the trial as open-label, and states that avelumab was started 4 to 10 weeks after the last chemotherapy dose. The main measure was overall survival — how long people lived.

Main result (2020). At one year, 71.3% of the avelumab group and 58.4% of the control group were alive. Median overall survival was 21.4 months against 14.3 months (hazard ratio for death 0.69, 95% confidence interval 0.56 to 0.86; P = 0.001). In people with PD-L1-positive tumors, one-year survival was 79.1% against 60.4% (hazard ratio 0.56). Median progression-free survival — time until the cancer grew, or death — was 3.7 against 2.0 months overall.

After at least two years (2023). With a median follow-up of 38.0 and 39.6 months in the two groups, overall survival remained longer with avelumab (hazard ratio 0.76, 95% confidence interval 0.63 to 0.91; P = 0.0036). 67 people (19.5%) had received avelumab for two years or more, and no new safety signals were found with the longer treatment. The label’s updated analysis gives median overall survival of 23.8 against 15.0 months.

Who the benefit was measured in. The label reports an updated hazard ratio of 0.69 in people with PD-L1-positive tumors and, in an exploratory analysis of PD-L1-negative tumors, 0.82 with a 95% confidence interval of 0.62 to 1.09. The label also notes that after stopping study treatment, 44% of the supportive-care group and 6% of the avelumab group received another PD-1 or PD-L1 antibody.

Side effects in the trial. Side effects of any cause occurred in 98.0% of the avelumab group and 77.7% of the control group; severe ones (grade 3 or higher) in 47.4% against 25.2%. The label reports serious adverse reactions in 28% of people on avelumab, one death from sepsis (0.3%), permanent stopping because of a side effect in 12%, and high-dose prednisone (40 mg a day or more) for an immune side effect in 9%. The most common side effects (20% or more) were fatigue, muscle and bone pain, urinary tract infection and rash.

Other treatments for this cancer are covered on the Bladder Cancer and Enfortumab Vedotin pages.

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JAVELIN Renal 101: With Axitinib in Kidney Cancer

Axitinib is a pill that blocks blood-vessel growth signals (a tyrosine kinase inhibitor). JAVELIN Renal 101 tested avelumab plus axitinib against sunitinib, a single blood-vessel-blocking pill that was then a standard first treatment.

How it was run. This phase 3 trial assigned 886 people with untreated advanced renal cell carcinoma at random to avelumab 10 mg/kg every 2 weeks plus axitinib 5 mg twice a day (442 people) or sunitinib 50 mg once a day for 4 weeks of every 6 (444 people). Its two main measures were progression-free survival and overall survival in people whose tumors were PD-L1-positive, who made up 560 of the 886 (63.2%).

First report (2019). In PD-L1-positive tumors, median progression-free survival was 13.8 months with the combination against 7.2 months with sunitinib (hazard ratio 0.61, 95% confidence interval 0.47 to 0.79). In everyone, it was 13.8 against 8.4 months (hazard ratio 0.69). Tumors shrank in 55.2% against 25.5% of the PD-L1-positive group. Overall survival was not yet mature: 37 and 44 people had died.

Final analysis (2025). After a minimum follow-up of 68 months, median overall survival was 44.8 against 38.9 months in everyone (hazard ratio 0.88, P = 0.0669) and 43.2 against 36.2 months in PD-L1-positive tumors (hazard ratio 0.86, P = 0.0755). The authors state that the survival analyses favoured the combination “but did not reach statistical significance,” and that later treatments may have affected the result. The label likewise states that the final overall-survival analysis “was not statistically significant” in either group. At 5 years, 12.0% of the combination group and 4.4% of the sunitinib group were alive without the cancer having grown, and responses lasting at least 5 years occurred in 16.4% against 9.2%. Response rates were 59.7% against 32.0% in the final report; the label, which counts responses confirmed by blinded central review, gives 51.4% against 25.7%.

Side effects in the trial. Severe treatment-related side effects (grade 3 or higher) occurred in 66.8% of the combination group and 61.5% of the sunitinib group in the final report. The label reports fatal adverse reactions in 1.8% of people on the combination (sudden cardiac death 1.2%, stroke, myocarditis and necrotizing pancreatitis 0.2% each), serious adverse reactions in 35%, and permanent stopping of one or both drugs in 22%. Liver injury was more frequent than with avelumab alone: raised liver enzymes reached grade 3 in 9% and grade 4 in 7%, and immune-mediated hepatitis was reported in 7%.

The other drug combinations for this cancer are covered on the Renal Cell Carcinoma and Kidney Cancer pages.

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How the Label Gives the Drug

The trials gave avelumab by body weight, at 10 mg/kg every 2 weeks. The current label gives a fixed dose instead:

The infusion runs through a fine 0.2-micron in-line filter. According to the label, the drug reaches steady blood levels after about 4 to 6 weeks, its terminal half-life is 6.1 days at the 10 mg/kg dose, and it is cleared by being broken down like other proteins. Mild to severe kidney impairment and mild or moderate liver impairment did not change its clearance in a clinically meaningful way; the effect of severe liver impairment is unknown.

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Immune-Mediated Side Effects and Their Rates on the Label

The label states that immune-mediated adverse reactions “may be severe or fatal” and “can occur in any organ system or tissue,” at any time after starting treatment and also after the drug has been stopped. It lists checks of liver enzymes, creatinine (a kidney marker) and thyroid function at the start and periodically during treatment. The rates below come from 1,854 people who received avelumab alone in the JAVELIN Merkel 200 and JAVELIN Solid Tumor trials:

The label lists rarer immune reactions, under 1%, that occurred with avelumab or with other PD-1/PD-L1 antibodies, some severe or fatal: heart muscle inflammation (myocarditis), pericarditis, inflammation of blood vessels, the pancreas, the brain and its linings, nerves and muscles, myasthenia gravis, Guillain-Barré syndrome, eye inflammation that can threaten sight, several blood disorders, and rejection of transplanted organs.

For moderate and severe immune reactions, the label describes withholding or permanently stopping the drug according to severity and giving corticosteroids (1 to 2 mg/kg a day of prednisone or an equivalent) until the reaction settles, then tapering over at least a month. In the Merkel cell trial, the label reports serious adverse reactions of any kind in 52% of 204 patients and permanent stopping because of a side effect in 27%. The most common side effects there (20% or more) were fatigue (47%), muscle and bone pain (29%), infusion-related reactions (26%), rash (25%), nausea (23%), constipation (22%), cough (22%) and diarrhea (21%).

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Infusion Reactions, Heart Events and Other Label Warnings

Infusion-related reactions. The label links its premedication instruction to these reactions. Infusion-related reactions occurred in 26% of people treated with avelumab, including 3 (0.2%) life-threatening (grade 4) and 10 (0.5%) severe (grade 3) reactions. Ninety-three percent of these people had received an antihistamine and acetaminophen beforehand. Fifteen percent of reactions began after the infusion had finished. The signs the label lists are fever, chills, flushing, low blood pressure, shortness of breath, wheezing, back pain, abdominal pain and hives. The label gives slowing or pausing the infusion for mild or moderate reactions and permanent stopping for severe or life-threatening ones.

Major heart and blood-vessel events with axitinib. In JAVELIN Renal 101, major adverse cardiovascular events occurred in 7% of people on avelumab plus axitinib, against 3.4% on sunitinib. They included death from heart causes (1.4%), severe heart attack (2.8%) and severe heart failure (1.8%). The median time to such an event was 4.2 months.

Stem cell transplants. The label warns that fatal and other serious complications, including graft-versus-host disease and liver vein blockage, can occur in people who receive a donor (allogeneic) stem cell transplant before or after a PD-1 or PD-L1 antibody.

Pregnancy and breastfeeding. Based on how the drug works, the label states that it can harm a fetus. In mice, blocking PD-L1 signalling disrupted the mother’s immune tolerance of the fetus and increased fetal loss. The label advises effective contraception during treatment and for at least one month after the last dose, and advises against breastfeeding for the same period. There is no information on whether avelumab passes into human milk.

Decisions about any cancer medicine belong with the treating oncology team.

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What Is Not Known

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Key Research Papers

  1. Kaufman HL, Russell J, Hamid O, Bhatia S, Terheyden P, D'Angelo SP, et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol. 2016;17(10):1374-1385. PubMed PMID: 27592805
  2. Kaufman HL, Russell JS, Hamid O, Bhatia S, Terheyden P, D'Angelo SP, et al. 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. J Immunother Cancer. 2018;6(1):7. PubMed PMID: 29347993
  3. D'Angelo SP, Bhatia S, Brohl AS, Hamid O, Mehnert JM, Terheyden P, et al. Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial. J Immunother Cancer. 2020;8(1):e000674. PubMed PMID: 32414862
  4. D'Angelo SP, Bhatia S, Brohl AS, Hamid O, Mehnert JM, Terheyden P, et al. Avelumab in patients with previously treated metastatic Merkel cell carcinoma (JAVELIN Merkel 200): updated overall survival data after >5 years of follow-up. ESMO Open. 2021;6(6):100290. PubMed PMID: 34715570
  5. D'Angelo SP, Russell J, Lebbé C, Chmielowski B, Gambichler T, Grob JJ, et al. Efficacy and Safety of First-line Avelumab Treatment in Patients With Stage IV Metastatic Merkel Cell Carcinoma: A Preplanned Interim Analysis of a Clinical Trial. JAMA Oncol. 2018;4(9):e180077. PubMed PMID: 29566106
  6. D'Angelo SP, Lebbé C, Mortier L, Brohl AS, Fazio N, Grob JJ, et al. First-line avelumab treatment in patients with metastatic Merkel cell carcinoma: 4-year follow-up from part B of the JAVELIN Merkel 200 study. ESMO Open. 2024;9(5):103461. PubMed PMID: 38744102
  7. Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, et al. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020;383(13):1218-1230. PubMed PMID: 32945632
  8. Powles T, Park SH, Caserta C, Valderrama BP, Gurney H, Ullén A, et al. Avelumab First-Line Maintenance for Advanced Urothelial Carcinoma: Results From the JAVELIN Bladder 100 Trial After ≥2 Years of Follow-Up. J Clin Oncol. 2023;41(19):3486-3492. PubMed PMID: 37071838
  9. Motzer RJ, Penkov K, Haanen J, Rini B, Albiges L, Campbell MT, et al. Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019;380(12):1103-1115. PubMed PMID: 30779531
  10. Choueiri TK, Penkov K, Uemura H, Campbell MT, Pal S, Kollmannsberger C, et al. Avelumab + axitinib versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma: final analysis of the phase III JAVELIN Renal 101 trial. Ann Oncol. 2025;36(4):387-392. PubMed PMID: 39706335
  11. Heery CR, O'Sullivan-Coyne G, Madan RA, Cordes L, Rajan A, Rauckhorst M, et al. Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial. Lancet Oncol. 2017;18(5):587-598. PubMed PMID: 28373007
  12. Ning YM, Suzman D, Maher VE, Zhang L, Tang S, Ricks T, et al. FDA Approval Summary: Atezolizumab for the Treatment of Patients with Progressive Advanced Urothelial Carcinoma after Platinum-Containing Chemotherapy. Oncologist. 2017;22(6):743-749. PubMed PMID: 28424325
  13. US prescribing information for avelumab injection, as published on DailyMed (US National Library of Medicine), version of September 2026. DailyMed label

PubMed Topic Searches

  1. PubMed: avelumab in Merkel cell carcinoma
  2. PubMed: avelumab maintenance in urothelial carcinoma
  3. PubMed: avelumab with axitinib in renal cell carcinoma
  4. PubMed: avelumab infusion-related reactions

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Connections

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