‘Radically different’ PI3Kδ inhibitor lacks hepatotoxicity
Adverse events occurring in more than 10% of patients included nausea (41%), diarrhea (32%), fatigue (32%), headache (23%), vomiting (23%), cough (21%), decreased appetite (17%), rash (17%), constipation (14%), hypokalemia (14%), anemia, dizziness, dyspnea, neutropenia, and pyrexia (12% each), and abdominal pain (11%).
The most common grade 3-4 toxicity was neutropenia, occurring in 11% of patients.
“But other than that, the bulk of the toxicities in terms of grade 3-4 events were relatively modest,” Dr O’Connor said. “[I]t’s worth pointing out that diarrhea grade 3-4 only occurred in about 2% of patients in the population.”
Approximately 50% of patients (n=31) have been on study for more than 6 months, and approximately 30% taking a higher dose level have been on study for 6 months or more. Twenty-five of 37 patients exposed to 800 mg or more of the micronized formulation currently remain on study.
“So this gives you a sense that it is a very well-tolerated drug, with patients staying on for extended periods of time,” Dr O’Connor said.
He added that time on study becomes relevant in assessing some of the gastrointestinal toxicities seen with other PI3Kδ inhibitors, where it seems the median time to gastrointestinal toxicity is beyond 6 months.
“So far, and I’m willing to concede it’s early, but with half the patients being treated for over 6 months, [diarrhea/colitis] seems to be much lower than the experience with the other PI3 kinase inhibitors,” Dr O’Connor said.
“I think one of the more important features of [TGR-1202], and one that allows me to think we might be able to integrate this drug a little more readily into various combination regimens, are the discontinuations due to other adverse events.”
“Only 4% treated with [TGR-1202] had discontinuations secondary to adverse events. [A]nd it looks like the efficacy is in line with what we’d expect with some of the other drugs, but this [study] is actively accruing still.” 
*Information in the abstract differs from that presented at the meeting.
