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
| Toxicity | Hold treatment for grade | Timing for restarting treatment |
|---|---|---|
|
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 | 2b | 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 Toxicityc | 3 or Severe | Toxicity resolves to Grade 0–1 |
| 4 | Permanently discontinue |
Note: Permanently discontinue for any severe or Grade 3 drug-related AE that recurs or any life-threatening event
a For participants who begin treatment with Grade 2 AST or ALT at Cycle 1 Day 1 of treatment, if AST or ALT increases by greater than or equal to 50% relative to baseline and lasts for at least 1 week then participants should be discontinued
b If symptoms resolve within one hour of stopping IMP infusion, the infusion may be restarted at 50% of the original infusion rate (e.g., from 100 mL/hr. to 50 mL/hr). Otherwise dosing will be held until symptoms resolve and the participant should be pre-medicated for the next scheduled dose
c Participants with intolerable or persistent Grade 2 drug-related AE may hold study medication at PI/delegate discretion