Bavencio

Bavencio Adverse Reactions

avelumab

Manufacturer:

Merck

Distributor:

Apex Pharma Marketing
Full Prescribing Info
Adverse Reactions
Summary of the safety profile: Avelumab is most frequently associated with immune-related adverse reactions. Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal of avelumab (see Description of selected adverse reactions as follows).
The safety of avelumab has been evaluated in 1,738 patients with solid tumours including metastatic MCC receiving 10 mg/kg every 2 weeks of avelumab in clinical studies. In this patient population, the most common adverse reactions with avelumab were fatigue (32.4%), nausea (25.1%), diarrhoea (18.9%), decreased appetite (18.4%), constipation (18.4%), infusion-related reactions (17.1%), weight decreased (16.6%), and vomiting (16.2%).
The most common Grade ≥ 3 adverse reactions were anaemia (6.0%), dyspnoea (3.9%), and abdominal pain (3.0%). Serious adverse reactions were immune-related adverse reactions and infusion-related reaction (see Precautions).
Tabulated list of adverse reactions: Adverse reactions reported for 88 patients with metastatic MCC treated with avelumab 10 mg/kg and adverse reactions reported for 1,650 patients in a phase I study in other solid tumours are presented in Table 5.
These reactions are presented by system organ class and frequency. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. (See Table 5.)

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Description of selected adverse reactions: Data for the following immune-related adverse reactions are based on 1,650 patients in the phase I study EMR100070-001 in other solid tumours and 88 patients in study EMR100070-003 who received avelumab (see Pharmacology: Pharmacodynamics under Actions).
The management guidelines for these adverse reactions are described in Precautions.
Immune-related pneumonitis: Across clinical studies, 1.2% (21/1,738) of patients developed immune-related pneumonitis. Of these patients there was 1 (0.1%) patient with a fatal outcome, 1 (0.1%) patient with Grade 4, and 5 (0.3%) patients with Grade 3 immune-related pneumonitis.
The median time to onset of immune-related pneumonitis was 2.5 months (range: 3 days to 11 months). The median duration was 7 weeks (range: 4 days to more than 4 months).
Avelumab was discontinued in 0.3% (6/1,738) of patients due to immune-related pneumonitis. All 21 patients with immune-related pneumonitis were treated with corticosteroids and 17 (81%) of the 21 patients were treated with high-dose corticosteroids for a median of 8 days (range: 1 day to 2.3 months). Immune-related pneumonitis resolved in 12 (57%) of the 21 patients at the time of data cut-off.
Immune-related hepatitis: Across clinical studies, 0.9% (16/1,738) of patients developed immune-related hepatitis. Of these patients, there were 2 (0.1%) patients with a fatal outcome, and 11 (0.6%) patients with Grade 3 immune-related hepatitis.
The median time to onset of immune-related hepatitis was 3.2 months (range: 1 week to 15 months). The median duration was 2.5 months (range: 1 day to more than 7.4 months).
Avelumab was discontinued in 0.5% (9/1,738) of patients due to immune-related hepatitis. All 16 patients with immune-related hepatitis treated with corticosteroids and 15 (94%) of the 16 patients received high-dose corticosteroids for a median of 14 days (range: 1 day to 2.5 months). Immune-related hepatitis resolved in 9 (56%) of the 16 patients at the time of data cut-off.
Immune-related colitis: Across clinical studies, 1.5% (26/1,738) of patients developed immune-related colitis. Of these patients, there were 7 (0.4%) patients with Grade 3 immune-related colitis.
The median time to onset of immune-related colitis was 2.1 months (range: 2 days to 11 months). The median duration was 6 weeks (range: 1 day to more than 14 months).
Avelumab was discontinued in 0.5% (9/1,738) of patients due to immune-related colitis. All 26 patients with immune-related colitis were treated with corticosteroids and 15 (58%) of the 26 patients received high-dose corticosteroids for a median of 19 days (range: 1 day to 2.3 months). Immune-related colitis resolved in 18 (70%) of 26 patients at the time of data cut-off.
Immune-related endocrinopathies: Thyroid disorders: Across clinical studies, 6% (98/1,738) of patients developed immune-related thyroid disorders, of which 90 (5%) patients with hypothyroidism, 7 (0.4%) with hyperthyroidism, and 4 (0.2%) with thyroiditis. Of these patients, there were 3 (0.2%) patients with Grade 3 immune-related thyroid disorders.
The median time to onset of thyroid disorders was 2.8 months (range: 2 weeks to 13 months). The median duration was not estimable (range: 1 day to more than 26 months).
Avelumab was discontinued in 0.1% (2/1,738) of patients due to immune-related thyroid disorders. Thyroid disorders resolved in 7 (7%) of the 98 patients at the time of data cut-off.
Adrenal insufficiency: Across clinical studies, 0.5% (8/1,738) of patients developed immune-related adrenal insufficiency. Of these patients, there was 1 (0.1%) patient with Grade 3.
The median time to onset of immune-related adrenal insufficiency was 2.5 months (range: 1 day to 8 months). The median duration was not estimable (range: 2 days to more than 6 months).
Avelumab was discontinued in 0.1% (2/1,738) of patients due to immune-related adrenal insufficiency. All 8 patients with immune-related adrenal insufficiency were treated with corticosteroids, 4 (50%) of the 8 patients received high-dose systemic corticosteroids (≥ 40 mg prednisone or equivalent) followed by a taper for a median of 1 day (range: 1 day to 24 days). Adrenal insufficiency resolved in 1 patient with corticoid treatment at the time of data cut-off.
Type 1 diabetes mellitus: Type 1 diabetes mellitus without an alternative aetiology occurred in 0.1% (2/1,738) of patients including two Grade 3 reactions that led to permanent discontinuation of avelumab.
Immune-related nephritis and renal dysfunction: Immune-related nephritis occurred in 0.1% (1/1,738) of patients receiving avelumab leading to permanent discontinuation of avelumab.
Immunogenicity: Of 1,738 patients treated with avelumab 10 mg/kg as an intravenous infusion every 2 weeks, 1,627 were evaluable for treatment-emergent anti-drug antibodies (ADA) and 96 (5.9%) tested positive. In ADA positive patients, there may be an increased risk for infusion-related reactions (about 40% and 25% in ADA ever-positive and ADA never-positive patients, respectively). Based on data available, including the low incidence of immunogenicity, the impact of ADA on pharmacokinetics, efficacy and safety is uncertain, while the impact of neutralizing antibodies (nAb) is unknown.
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