Table 3 Summary of the physicians’ guidelines for IMP’s temporary interruption and permanent discontinuation in case of immune-related adverse events. PI: principal Investigator

Diarrhoea/

Colitis

2–3

Toxicity resolves to Grade 0–1

4

Permanently discontinue

AST, ALT, or Increased Bilirubin

2

Toxicity resolves to Grade 0–1

3–4

Permanently discontinue (see exception below)^a

Type 1 diabetes mellitus (if new onset) or Hyperglycaemia

T1DM or

3–4

Hold the IMP for new onset Type 1 diabetes mellitus or Grade 3–4 hyperglycemia associated with evidence of beta cell failure

Hypophysitis

2–4

Toxicity resolves to Grade 0–1. Therapy with IMP can be continued while endocrine replacement therapy is instituted

Hyperthyroidism

3

Toxicity resolves to Grade 0–1

4

Permanently discontinue

Hypothyroidism

N/A

Therapy with IMP can be continued while thyroid replacement therapy is instituted

Infusion Reaction

2^b

Toxicity resolves to Grade 0–1

3–4

Permanently discontinue

Pneumonitis

2

Toxicity resolves to Grade 0–1

3–4

Permanently discontinue

Renal Failure or Nephritis

2

Toxicity resolves to Grade 0–1

3–4

Permanently discontinue

All Other Drug-Related Toxicity^c

3 or Severe

Toxicity resolves to Grade 0–1

4

Permanently discontinue