Innovation Pharmaceuticals Inc (IPIX)

[BonelessCat]

First there is the dose limiting toxicity (DLT) and then the maximum tolerated dose (MTD) is confirmed.

In any cohort where one or more severe side effects, adverse events or AEs, appear in one or more of the 3 patients, the protocol states that a DLT is declared and the following cohort returns to the previous dose level where no AEs were observed. So, if cohort 8 doses at 210 mg/m2, and AEs appear, then the next cohort would return to 165 mg/m2 and the cohort expands to 6 patients. If no further dose limiting AEs are observed then that dose level becomes the MTD, maximum tolerated dose.

Ideally, and according to the window of efficacy stated by Dr Menon as 100 to 200 mg/m2, dose escalation would continue through to the 9th cohort, or the next dose level above cohort 8. If 8 is approved, then it should be at or above 200 mg/m2, so if 9 encounters the DLT, then the MTD will likely be > or = 200 mg/m2.