Table 3

Time to onset and resolution of immune-mediated adverse events

IMAE by categoryAll treated patients who experienced at least 1 IMAE*
Median (range) time to onset, weeksMedian (range) time to resolution, weeks
Any gradeGrade 3/4Any gradeGrade 3/4
Rashn=27
5.3 (0.3–80.4)
n=7
4.0 (1.1–80.4)
n=17
12.6 (1.9–156.1)
n=2
NR (5.3–126.9+)
Hypothyroidism and thyroiditis†n=21
12.1 (2.3–25.1)
n=0
n=5
NR (3.7–156.7+)
n=0
Diarrhoea/colitisn=15
26.1 (1.4–115.7)
n=8
21.8 (1.7–115.7)
n=11
5.9 (0.9–141.7+)
n=7
2.7 (0.7–117.0+)
Adrenal insufficiency†n=9
33.9 (16.1–54.0)
n=3
51.4 (21.0–54.0)
n=4
NR (0.4–130.6+)
n=2
0.7 (0.4–89.0+)
Hyperthyroidism†n=8
6.3 (4.0–39.1)
n=0
n=8
12.1 (5.1–134.7+)
n=0
Hepatitisn=7
37.1 (2.0–80.7)
n=3
8.4 (2.0–82.1)
n=1
3.0 (NC)
n=1
3.0 (NC)
Diabetes mellitus†n=6
29.1 (4.3–58.6)
n=4
13.6 (4.3–39.1)
n=2
NR (0.4–141.3+)
n=2
NR (0.4–141.3+)
Hypersensitivityn=6
4.8 (4.0–8.1)
n=0
n=6
0.1 (0.1–0.1)
n=0
Pneumonitisn=3
12.7 (11.1–64.0)
n=1
12.7 (NC)
n=3
14.9 (0.9–17.3)
n=1
0.9 (NC)
Hypophysitis†n=3
33.9 (25.9–52.7)
n=0
n=0
n=0
Nephritis and renal dysfunctionn=2
16.4 (3.7–29.1)
n=0
n=2
6.0 (4.7–7.3)
n=0
  • *Includes events reported between the first dose and 100 days after last dose of study therapy. Time to onset was calculated from the first dosing date to the IMAE event onset date. Time to resolution was calculated from the IMAE onset date to IMAE end date. If an IMAE was ongoing at the time of analysis, the time to resolution was censored at the last contact date. Patients who experienced an IMAE without worsening from baseline grade were excluded from time to resolution analysis. Events without a stop date or with a stop date equal to the date of death were considered unresolved. For each patient, the longest duration of IMAEs where immune-modulating medication was initiated is considered.

  • †Considered endocrine IMAEs.

  • +, censored value; IMAE, immune-mediated adverse event; NC, not calculated; NR, not reached.