Drugs

, Volume 77, Issue 8, pp 929–937 | Cite as

Avelumab: First Global Approval

AdisInsight Report

Abstract

Avelumab (Bavencio®) is an intravenously administered programmed cell death ligand-1-blocking human antibody initially developed by EMD Serono Inc. (the biopharmaceutical division of Merck KGaA, Darmstadt, Germany) [now jointly developed and commercialized by EMD Serono Inc. and Pfizer] for the treatment of various tumours. It has received accelerated approval in the USA for the treatment of metastatic Merkel cell carcinoma (mMCC) in adults and paediatric patients aged ≥12 years. The marketing authorization application for avelumab in the treatment of mMCC is undergoing regulatory review in the EU, the biologics license application for avelumab in the treatment of urothelial carcinoma is undergoing priority review by the FDA, and avelumab is in various stages of development internationally for a variety of cancers. This article summarizes the milestones in the development of avelumab leading to this first approval for mMCC.

1 Introduction

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine cutaneous neoplasm that is considered the deadliest of skin cancers, with a mortality rate three times that of melanoma, and typically occurs in sun-exposed skin in elderly and/or immunosuppressed individuals [1, 2, 3]. Merkel cell polyomavirus (MCV) is present in ≈80% of cases, and programmed cell death ligand-1 (PD-L1) is expressed frequently on MCC cells and surrounding immune cells [3, 4, 5]. PD-L1 binds to PD receptor-1 (PD-1) on cytotoxic T cells and inhibits their tumour-killing activity [4].

MCC has a propensity for local recurrence and regional nodal or distant metastases, and 67–74% of patients with systemic metastases die, usually within 6 months of metastases detection [1]. Until recently, there were no approved treatments available to treat non-resectable, recurrent, or metastatic MCC (mMCC) [6].

Avelumab (Bavencio®) is an intravenously administered PD-L1-blocking human antibody developed by EMD Serono Inc. (the biopharmaceutical division of Merck KGaA, Darmstadt, Germany) that received accelerated approval in the USA on 23 March 2017 for the treatment of mMCC in adults and paediatric patients aged ≥12 years [7, 8, 9]. It is the first treatment that has been approved for this indication in the USA [8].

The recommended dosage of avelumab is 10 mg/kg administered as an intravenous infusion over 60 min fortnightly until disease progression or unacceptable toxicity [7]. Patients should be premedicated with acetaminophen (paracetamol) and an antihistamine for the first four infusions and as needed thereafter [7].

Key development milestones for avelumab in metastatic Merkel cell carcinoma. BLA biologics license application, COMP Committee for Orphan Medicinal Products, CRADA Cooperative Research and Development Agreement, EMA European Medicines Agency, MAA Marketing Authorisation Application, MCC Merkel cell carcinoma, NCI National Cancer Institute

The marketing authorization application for avelumab in the treatment of mMCC is under regulatory review in the EU [10], and phase II development is underway in Australia, Japan and Switzerland for mMCC [11]. In February this year, the FDA accepted for priority review the biologics license application for avelumab in the treatment of metastatic urothelial carcinoma [12]. In addition, in various countries worldwide, avelumab is under phase III development for breast cancer, diffuse large B cell lymphoma, gastric cancer, head and neck cancer, non-small cell lung cancer (NSCLC), ovarian cancer and renal cell carcinoma, phase II development for endometrial cancer, gestational trophoblastic disease, glioblastoma, intestinal cancer, nasopharyngeal cancer, recurrent respiratory papillomatosis, and thymoma, phase I/II development for fallopian tube cancer and peritoneal cancer, and phase I development for acute myeloid leukaemia, Hodgkin’s disease, and solid tumours [11].

1.1 Company Agreements

In November 2014, Merck KGaA and Pfizer entered into a global agreement to jointly develop and commercialize avelumab [13, 14]. Under the terms of the agreement, Merck KGaA receives an upfront payment and is eligible to receive regulatory and commercial milestone payments, and both companies jointly fund the development and commercialization of avelumab and share all revenues generated from the collaboration. Of note, this collaboration also includes combining expertise and resources to advance an anti-PD-1 antibody developed by Pfizer to phase I trials, and co-promoting Pfizer’s crizotinib (Xalkori®) in the USA and other key markets [13, 14].

The Merck KGaA-Pfizer alliance entered into collaborative agreements with Syndax Pharmaceuticals Inc. in January 2016 to investigate the use of avelumab in combination with entinostat in heavily pre-treated, recurrent ovarian cancer [15], Verastem in March 2016 to investigate the use of avelumab in combination with VS-6063 in advanced ovarian cancer [16], Transgene in October 2016 to investigate the use of avelumab in combination with TG4001 for human papilloma virus-positive head and neck squamous cell carcinoma following failure of standard therapy [17], and Debiopharm International in October 2016 to investigate the use of avelumab in combination with Debio 1143 in advanced or metastatic NSCLC [18]. In addition, Merck KGaA entered into a collaborative agreement with Vaccinex Inc. in October 2016 to investigate the use of avelumab with VX15/2503 in advanced NSCLC [19], and Pfizer entered into a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) in November 2016 to investigate avelumab as well as two other immunotherapy agents (OX40, and utomilumab) in preclinical and clinical studies [20]. Phase I/Ib [16, 18], I/II [17] and Ib/II [15, 19] studies have been planned.

2 Scientific Summary

2.1 Pharmacodynamics

Avelumab is a human IgG1 lambda monoclonal antibody that binds PD-L1, thereby blocking the interaction of PD-L1 with the receptors PD-1 and B7.1 found on T cells and antigen-presenting cells [7]. Binding of PD-L1 to the PD-1 and B7.1 receptors suppresses cytotoxic T-cell activity, and blocking this leads to the restoration of immune responses (e.g. anti-tumour immune responses) [7]. In syngeneic mouse models, decreased tumour growth resulted from blocking PD-L1 activity [7]. Avelumab differs from other PD-L1/PD-1 checkpoint-blocking antibodies in that it has been shown in vitro to induce antibody-dependent cell-mediated cytotoxicity (ADCC) [7, 21]. The PD-L1 interaction-blocking activity of avelumab is thought to enable T-cell activation and the adaptive immune system [21, 22]. By retaining a native Fc-region, avelumab is thought to engage the innate immune system and induce ADCC [21, 22]. So far, ADCC has not been shown to contribute to the clinical activity of avelumab [23], but ADCC might contribute to the activity of avelumab as shown in preclinical models [6, 24].

2.2 Pharmacokinetics

Avelumab exposure, over the dosage range of 1–20 mg/kg every 2 weeks, increased dose-proportionally in 1629 patients who received avelumab in that dosage range [7]. Avelumab reached steady state after ≈4 to 6 weeks (2–3 cycles) of repeated dosing. For a subject receiving avelumab 10 mg/kg, the mean volume of distribution at steady state is 4.72 L. Avelumab undergoes proteolytic degradation as the primary mechanism of elimination. In patients with solid tumours receiving avelumab 10 mg/kg, the terminal half-life was 6.1 days, and the total systemic clearance was 0.59 L/day [based on population pharmacokinetic (PK) analyses]. In patients with MCC, avelumab clearance was found to decrease over time, with a mean maximal reduction (% coefficient of variation) of ≈41.7% (40.0%) from baseline (based on a post hoc analysis). Age, gender, race, PD-L1 expression status, tumour burden, the presence of renal impairment (mild, moderate or severe) and the presence of hepatic impairment (mild or moderate) have no clinically meaningful effect on the clearance of avelumab. Bodyweight had a positive correlation with the total systemic clearance of avelumab (based on population PK analyses), and the effect of severe hepatic impairment on avelumab PK is unknown [7].

Features and properties of avelumab

Alternative names

Bavencio®; Anti-PD-L1 monoclonal antibody-EMD Serono; Anti-PD-L1 monoclonal antibody-Merck; MSB-0010718C; PF-06834635

Class

Antineoplastics, monoclonal antibodies

Mechanism of action

CD274 antigen inhibitor, immunomodulator

Route of administration

IV infusion

Pharmacodynamics

Binds PD-L1 and blocks the interaction of PD-L1 with PD-1 and B7.1, resulting in immune response restoration

Pharmacokinetics

Displays dose-proportional pharmacokinetics; steady state reached in ≈4 to 6 weeks; Vss = 4.72 L; terminal t1/2 = 6.1 days; systemic CL = 0.59 L/day

Adverse events (overall)

 Most frequent

Decreased appetite, diarrhoea, fatigue, infusion-related reaction, musculoskeletal pain, nausea, rash, peripheral oedema

 Occasional or rare

Immune-mediated events

ATC codes

 WHO ATC code

J05A (Direct acting antivirals), L01X-C (Monoclonal antibodies)

 EphMRA ATC code

J5B (Antivirals, excluding anti-HIV products), L1G (Monoclonal antibody antineoplastics)

Chemical name

C6374-H9898-N1694-O2010-S44 (non-glycosylated)

CL clearance, IV intravenous, PD-1 programmed cell death receptor-1, PD-L1 programmed cell death ligand-1, t1/2 half-life, Vss volume of distribution at steady state

2.3 Therapeutic Trials

JAVELIN, the international clinical development programme for avelumab, encompasses at least 30 clinical programs, involving >4000 patients, across >15 tumour types [25], regardless of PD-L1 expression [6, 26]. The first of these trials is JAVELIN Solid Tumor, from which avelumab 10 mg/kg every 2 weeks was chosen in the phase Ia, dose-escalation trial as the dosage for further study [23]. The ongoing dose-expansion part (phase Ib) of the trial comprises 16 different cohorts (i.e. a wide range of advanced solid tumours), and is discussed further in Sect. 2.3.2 [27]. Based on the data from this trial, a number of phase II and III trials have been initiated, including JAVELIN Merkel 200, on which FDA approval of avelumab for mMCC was based (Sect. 2.3.1) [28].

2.3.1 Merkel Cell Carcinoma

Avelumab treatment was associated with durable responses in patients with chemotherapy-refractory mMCC in an open-label, multinational, phase II JAVELIN Merkel 200 trial (n = 88) [NCT02155647] [6]. At baseline, patients had a median age of 72.5 years (range 64.5–77.0 years), a median time since diagnosis of mMCC of 10.4 months (range 6.3–17.2 months), Eastern Cooperative Oncology Group (ECOG) performance scores of 0 (56% of patients) or 1 (44%) and distant metastases that had been treated with one (n = 57) or ≥2 (n = 31) previous lines of therapy. Visceral metastasis was present in 53% of patients. Patients were not selected based on PD-L1 status (66% of patients were positive, 18% were negative and 16% were not assessable) or MCV status (52% of patients were positive, 35% were negative and 13% were not assessable) at baseline [6].

Patients received an intravenous infusion of avelumab 10 mg/kg over 1 h, every 2 weeks until disease progression, unacceptable toxicity or other reason for withdrawal [6]. The primary efficacy endpoint was confirmed best overall response [defined as a complete or partial response, or stable or progressive disease, assessed by an independent review committee and according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1] [6].

In JAVELIN Merkel 200, at a median follow-up of 10.4 months (primary analysis; data cut-off date of 3 March 2016), 32% of patients had an objective response (OR; 9% with a complete response and 23% with a partial response); 10% of patients had stable disease and 36% of patients had progressive disease [6]. Among patients with an OR, responses were noted at the first post-baseline assessment in 79% of patients, and responses were ongoing at the time of analysis in 82% of patients. Responses to avelumab occurred regardless of PD-L1 expression or MCV status (post hoc subgroup analyses). At the time of follow-up, the median duration of response (time from first complete or partial response to progressive disease or death) had not been reached (at least 2.8–17.5 months; 95% CI 8.3 months–not estimable). Median progression-free survival (PFS) was 2.7 months, and median overall survival (OS) was 11.3 months [6].

2.3.2 Other Malignancies

The open-label, multinational, dose-expansion phase Ib part of JAVELIN Solid Tumor (NCT01772004) enrolled patients with locally advanced or metastatic solid tumours in 16 different expansion cohorts (including, but not limited to, breast cancer, pancreatic cancer, ovarian cancer, urothelial cancer, mesothelioma and NSCLC) [23, 26, 27]. All patients were not selected based on PD-L1 expression, and received intravenous avelumab 10 mg/kg every 2 weeks until disease progression, unacceptable toxicity or other reason for withdrawal [26]. Although the primary endpoint of the trial was safety [27], avelumab demonstrated preliminary efficacy in multiple tumour types.

For example, in the advanced NSCLC (previously treated) cohort of JAVELIN Solid Tumor (n = 184), at a median follow-up of 8.8 months, 50% of patients achieved disease control [12% of patients had a confirmed OR (one patient with a complete response and 21 patients with partial responses), and 38% of patients had stable disease] [27]. Responses occurred regardless of PD-L1 expression status or tumour histology. Among patients with an OR, responses were maintained for ≥24 weeks in 83% of patients (95% CI 54–94) by Kaplan–Meier estimates. The median duration of response had not been reached (at least 0.1–54 weeks; 95% CI 48.1–not evaluable) at the time of follow-up. Median PFS was 11.6 weeks according to RECIST version 1.1, and median OS was 8.4 months [27].

Preliminary efficacy data showing various rates of OR are also available for the following JAVELIN Solid Tumor cohorts: advanced NSCLC (not previously treated for advanced disease) [29], advanced gastric or gastroesophageal junction cancer (as first-line maintenance or second-line treatment) [30], metastatic urothelial carcinoma [31], advanced adrenocortical carcinoma [32], advanced thymic epithelial tumour [33], locally advanced or metastatic breast cancer [34], recurrent/refractory ovarian cancer [35], and advanced unresectable mesothelioma [36].

JAVELIN Solid Tumor JPN (NCT01943461) is an open-label, phase Ib trial of avelumab in Japanese patients with advanced solid tumours that consists of a dose-escalation part, as well as a dose-expansion part [37, 38]. Data are available for 20 patients with advanced gastric or gastroesophageal junction adenocarcinoma who received intravenous avelumab 10 mg/kg every 2 weeks in the dose expansion part of the study [38]. At a median follow-up of 6 months, the disease control rate (PR and stable disease) was 65.0% based on three patients with confirmed partial responses [38].

JAVELIN Renal 100 (NCT02493751) is an open-label, multicentre, phase Ib trial that examines the use of intravenous avelumab with oral axitinib as first-line therapy in patients with advanced renal cell carcinoma [39]. Data are available for six patients who received avelumab 10 mg/kg every 2 weeks with axitinib 5 mg twice daily in the dose-expansion part of the trial [40]. After a median duration of treatment of 17 weeks for avelumab and 16.3 weeks for axitinib, five patients had a confirmed partial response, and one patient had stable disease [40].

Key clinical trials of avelumab

Drug(s)

Indication

Phase

Status

Location(s)

Identifier

Sponsor(s)

JAVELIN trials

 Avelumab

Solid tumours

Ia/b

Recruiting (Ib)

Multinational

JAVELIN Solid Tumor; NCT01772004; EudraCT 2013-002834-19

EMD Serono

 Avelumab

Locally advanced or metastatic solid tumours

Ib

Ongoing

Japan

JAVELIN Solid Tumor JPN; NCT01943461

Merck KGaA

 Avelumab, Axitinib

Advanced renal cell cancer

Ib

Recruiting

Multinational

JAVELIN Renal 100; NCT02493751; EudraCT 2015-001137-25

Pfizer

 Avelumab

Previously treated, relapsed or refractory classical Hodgkin’s lymphoma

Ib

Recruiting

Multinational

JAVELIN HODGKINS; NCT02603419; EudraCT 2015-002636-41

Pfizer

 Avelumab, PF-05082566, PF-04518600, PD 0360324

Locally advanced or metastatic solid tumours

Ib/II

Recruiting

Multinational

JAVELIN Medley; NCT02554812; EudraCT 2015-002552-27

Pfizer

 Avelumab, PF-06463922, crizotinib

Locally advanced or metastatic NSCLC

Ib/II

Recruiting

Multinational

JAVELIN Lung 101; NCT02584634; EudraCT 2015-001879-43

Pfizer

 Avelumab

Metastatic MCC

II

Recruiting

Multinational

JAVELIN Merkel 200; NCT02155647; EudraCT2014-000445-79

EMD Serono

 Avelumab, utomilumab, rituximab, azacitidine, bendamustine, gemcitabine, oxaliplatin

Relapsed/refractory diffuse large B-cell lymphoma

Ib/III

Recruiting

Multinational

JAVELIN DLBCL; NCT02951156; EudraCT 2016-002904-15

Pfizer, EMD Serono

 Avelumab, docetaxel

PD-L1 positive, stage IIIb/IV or recurrent NSCLC

III

Ongoing

Multinational

JAVELIN Lung 200; NCT02395172; EudraCT 2014-005060-15

EMD Serono, Merck KGaA

 Avelumab, pemetrexed, paclitaxel, gemcitabine, carboplatin, cisplatin

Recurrent or stage IV PD-L1-positive NSCLC

III

Recruiting

Multinational

JAVELIN Lung 100; NCT02576574; EudraCT 2015-001537-24

EMD Serono, Merck KGaA

 Avelumab, pegylated liposomal doxorubicin

Platinum-resistant/refractory ovarian cancer

III

Recruiting

Multinational

JAVELIN Ovarian 200; NCT02580058; EudraCT 2015-003091-77

Pfizer

 Avelumab, oxaliplatin, 5-fluorouracil, leucovorin, capecitabine, BSC

Locally advanced or metastatic gastric or gastroesophageal junction cancer

III

Recruiting

Multinational

JAVELIN Gastric 100; NCT02625610; EudraCT 2015‐003300‐23

EMD Serono, Merck KGaA

 Avelumab, irinotecan, paclitaxel, BSC

Locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction

III

Recruiting

Multinational

JAVELIN Gastric 300; NCT02625623; EudraCT 2015-003301-42

EMD Serono, Merck KGaA

 Avelumab + axitinib, sunitinib

Advanced renal cell carcinoma (previously untreated)

III

Recruiting

Multinational

JAVELIN Renal 101; NCT02684006; EudraCT 2015-002429-20

Pfizer

 Avelumab, BSC

Locally advanced or metastatic urothelial cancer

III

Recruiting

Multinational

JAVELIN Bladder 100; NCT02603432; EudraCT 2015-003262-86

Pfizer

 Avelumab, carboplatin, paclitaxel

Epithelial ovarian cancer

III

Recruiting

Multinational

JAVELIN Ovarian 100; NCT02718417; EudraCT 2015-003239-36

Pfizer

Avelumab, SoC chemoradiotherapy

Locally advanced SCC of the head and neck

III

Recruiting

Multinational

JAVELIN Head and Neck 100; NCT02952586; EudraCT 2016-001456-21

Pfizer

Other trials

 Avelumab

Advanced or metastatic adenocarcinoma of the small intestine

I (or II)a

Recruiting

USA

NCT03000179

Vanderbilt-Ingram Cancer Center, NCI, EMD Serono

 Avelumab + defactinib

Recurrent or resistant epithelial ovarian cancer (epithelial ovarian, fallopian tube or peritoneal cancer)

I/Ib

Recruiting

USA

NCT02943317

Verastem, Inc.

 Avelumab + cetuximab + radiotherapy, then avelumab maintenance

Locally advanced SCC of the head and neck

Ib

Recruiting

Netherlands

NCT02938273

The Netherlands Cancer Institute, Merck KGaA

 Avelumab + M9241 (NHS-IL12)

Locally advanced, metastatic or unresectable solid tumours

Ib

Recruiting

USA

COMBO; NCT02994953

EMD Serono, Merck KGaA

 Avelumab + 5-azacytidine

Refractory/relapsed acute myeloid leukaemia

Ib/II

Recruiting

USA

NCT02953561; NCI-2016-01924

M. D. Anderson Cancer Center, Pfizer

 Avelumab + localized RT or recombinant interferon-β ± cellular adoptive immunotherapy

Metastatic MCC

I/II

Recruiting

USA

NCT02584829

Fred Hutchinson Cancer Research Center, EMD Serono, NCI

 Avelumab + SBRT

Early stage NSCLC

I/II

Recruiting

USA

NCT03050554

University of California, San Diego, Pfizer

 Avelumab

Recurrent/metastatic EBV-related nasopharyngeal carcinoma

II

Recruiting

USA

NCT02875613

University of California, San Diego, Pfizer

 Avelumab

Recurrent respiratory papillomatosis

II

Recruiting

USA

NCT02859454

NCI

 Avelumab

Recurrent or metastatic endometrial cancer

II

Recruiting

USA

NCT02912572

Dana-Farber Cancer Institute, Pfizer

 Avelumab

Chemo-resistant gestational trophoblastic neoplasias

II

Ongoing

France

TROPHIMMUN; EudraCT 2016-002322-37

Hospices Civils de Lyon, Merck

 Avelumab

Recurrent or progressive osteosarcoma

II

Recruiting

USA

NCT03006848

St. Jude Children’s Research Hospital, NCI

 Avelumab + hypofractionated radiation therapy

Glioblastoma

II

Recruiting

USA

NCT02968940

New York University School of Medicine, EMD Serono

 Avelumab + Ad-CEA vaccine + SoC, SoC

Metastatic colorectal cancer

II

Recruiting

USA

QUILT-2.004; NCT03050814

NCI

 Avelumab

Relapsed or refractory thymoma and thymic carcinoma

II

Recruiting

USA

NCT03076554

NCI

 Avelumab + temozolomide following radiotherapy

Glioblastoma multiforme

II

Recruiting

Canada

NCT03047473

Clinique Neuro-Outaouais

 Avelumab

High-risk triple-negative breast cancer

III

Recruiting

Italy

A-BRAVE; NCT02926196; EudraCT 2016-000189-45

Instituto Oncologico Veneto IRCCS, the University of Padova

BSC best supportive care, EBV Epstein-Barr virus, MCC Merkel cell carcinoma, NA not available, NCI National Cancer Institute, NSCLC non-small cell lung cancer, PD-L1 programmed death ligand 1, SoC standard of care, SCC squamous cell carcinoma, SBRT stereotactic body radiation therapy

aReferred to as a phase I, as well as a phase II pilot study [42]

2.4 Adverse Events

Avelumab had a manageable safety profile in clinical trials. For example, in JAVELIN Merkel 200 (primary analysis), treatment-related adverse events (TRAEs) occurred in 70.5% of patients, the majority of which were low grade events (grade 1–2 in 65.9% of patients, grade 3 in 4.5%) [6]. The most commonly occurring TRAEs of any grade (occurring in >10% of patients) were fatigue (24% of patients) and infusion-related reactions (17%); these were all grade 1–2 events, and the infusion reactions generally resolved on the same day with the use of supportive medications. Potential immune-mediated TRAEs, which were identified in <13% of patients [diarrhoea, hyperthyroidism, hypothyroidism, pneumonitis, type 1 diabetes mellitus, nephritis, rash (all grade 1 or 2), or grade 3 increased aminotransferase], were manageable. Serious TRAEs (chondrocalcinosis, enterocolitis, increased aminotransferases, infusion-related reaction, intestinal nephritis or synovitis) occurred in 6% of patients. TRAEs led to treatment discontinuation in one patient (grade 2 elevated aminotransferase), and there were no treatment-related deaths [6].

Avelumab treatment can result in severe and fatal immune-mediated adverse events [7]. They can involve any organ system, and although they generally manifest during treatment, some can occur after treatment discontinuation. Across 1738 patients who received avelumab in JAVELIN Solid Tumor and JAVELIN Merkel 200, immune-mediated events included, but were not limited to, pneumonitis (1.2% of patients), hepatitis (0.9%), colitis (1.5%), adrenal insufficiency (0.5%), thyroid disorders (6%), type 1 diabetes mellitus (no other aetiology; 0.1%), and nephritis (0.1%); these included events ranging from grades 3–5. There is also a risk of severe or life-threatening infusion-related adverse events. Infusion-related adverse events occurred in 25% of patients in the pooled population (439 of 1738 patients); these include grade 3 (0.5% of patients) and grade 4 (0.2%) events. In terms of treatment-emergent anti-drug antibodies (ADA), among evaluable patients (1558 of 1738 patients), 4.1% of patients tested positive. However, the PK profile of avelumab and the risk of infusion-related reactions did not appear to be altered by the emergence of ADAs [7].

2.5 Companion Diagnostic

In September 2015, Merck and Pfizer entered into a collaborative agreement with Dako, an Agilent Technologies company, to develop a potential companion diagnostic test (CDx) for use with avelumab [41]. This CDx is to assess levels of PD-L1 protein expression in tumour tissue, as well as the microenvironment of the tumour tissue, including tumour-associated immune cells. The investigational CDx has been included in protocols of ongoing avelumab clinical trials [41].

2.6 Ongoing Clinical Trials

The JAVELIN programme is ongoing, and numerous studies are ongoing in solid tumours, as well as in haematological malignancies.

3 Current Status

Avelumab received its first approval on 23 March 2017 for the treatment of metastatic mMCC in adults and paediatric patients aged ≥12 years in the USA [7, 8].

Notes

Disclosure

The preparation of this review was not supported by any external funding. During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. E. S. Kim is a salaried employee of Adis, Springer SBM.

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Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

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