ith an investigational gp100 peptide vaccine (gp100), and 132 patients (median age 57 years, 54% male) received gp100 peptide vaccine alone. Patients in the study received a median of 4 doses (range: 1–4 doses). Yervoy was discontinued for adverse reactions in 10% of patients.
The most common adverse reactions (≥5%) in patients who received Yervoy at 3 mg/kg were fatigue, diarrhea, pruritus, rash, and colitis.
Table 1 presents selected adverse reactions from Study 1, which occurred in at least 5% of patients in the Yervoy-containing arms and with at least 5% increased incidence over the control gp100 arm for all-grade events and at least 1% incidence over the control group for Grade 3–5 events.
Table 1: Selected Adverse Reactions in Study 1 a Incidences presented in this table are based on reports of adverse events regardless of causality.
Percentage (%) of Patientsa
Yervoy
3 mg/kg
n=131 Yervoy
3 mg/kg+gp100
n=380 gp100
n=132
System Organ Class/
Preferred Term Any
Grade Grade
3–5 Any
Grade Grade
3–5 Any
Grade Grade
3–5
Gastrointestinal Disorders
Diarrhea 32 5 37 4 20 1
Colitis 8 5 5 3 2 0
Skin and Subcutaneous Tissue Disorders
Pruritus 31 0 21 <1 11 0
Rash 29 2 25 2 8 0
General Disorders and Administration Site Conditions
Fatigue 41 7 34 5 31 3
Table 2 presents the per-patient incidence of severe, life-threatening, or fatal immune-mediated adverse reactions from Study 1.
Table 2: Severe to Fatal Immune-mediated Adverse Reactions in Study 1 a Including fatal outcome.
b Including intestinal perforation.
c Underlying etiology not established.
Percentage (%) of Patients
Yervoy
3 mg/kg
n=131 Yervoy
3 mg/kg+gp100
n=380
Any Immune-mediated Adverse Reaction 15 12
Enterocolitisa,b 7 7
Hepatotoxicitya 1 2
Dermatitisa 2 3
Neuropathya 1 <1
Endocrinopathy 4 1
Hypopituitarism 4 1
Adrenal insufficiency 0 1
Other
Pneumonitis 0 <1
Meningitis 0 <1
Nephritis 1 0
Eosinophiliac 1 0
Pericarditisa,c 0 <1
Across clinical studies that utilized Yervoy doses ranging from 0.3 to 10 mg/kg, the following adverse reactions were also reported (incidence less than 1% unless otherwise noted): urticaria (2%), large intestinal ulcer, esophagitis, acute respiratory distress syndrome, renal failure, and infusion reaction.
Based on the experience in the entire clinical program for melanoma, the incidence and severity of enterocolitis and hepatitis appear to be dose dependent.
Immunogenicity
In clinical studies, 1.1% of 1024 eva luable patients tested positive for binding antibodies against ipilimumab in an electrochemiluminescent (ECL) based assay. This assay has substantial limitations in detecting anti-ipilimumab antibodies in the presence of ipilimumab. Infusion-related or peri-infusional reactions consistent with hypersensitivity or anaphylaxis were not reported in these 11 patients nor were neutralizing antibodies against ipilimumab |
