Dose Escalation
nausea, DLTs, diarrhea, toxicity, tremor, stoma, retching, hypersensitivity
HYPERSENSITIVITY
In cohorts 1 (100 mg BID) and 2 (200 mg BID) no DLTs or other safety concerns were seen as concluded by the SRC. In cohort 3 (400 mg BID) also no DLTs were reported, but 2 out of 3 patients required a dose reduction due to treatment-related toxicity and 6 TEAEs led to OMO-1 treatment discontinuation in 2 patients (66.7%). In one of these 2 patients, the TEAEs leading to discontinuation were drug-related nausea, increased bilirubin, increased creatinine, and diarrhea (increased stoma output) (CTCAE grade 2). The other patient was discontinued due to hypersensitivity to OMO-1 (CTCAE grade 2; retching and tremor after administration) after a previous dose reduction due to drug-related flu-like symptoms (CTCAE grade 3). Although these TEAES were not reported as formal DLTs, further treatment at that dose level was precluded as decided by the SRC. In addition, the planned dose level of 600 mg BID was replaced by a lower dose level of 250 mg BID (cohort 4). No DLTs or significant safety concerns were seen in cohort 4. Cohort 5 (350 mg BID) was the final dose-escalation. However, the nature of the AEs reported in the 400 mg BID and 350 mg BID, along with the high rate of TEAEs leading to withdrawal resulted in the SRC deciding that these doses were not in keeping with long term dosing; therefore, 250 mg BID was chosen as the monotherapy RP2D.