ESMO 2020 | Update on the NAVIGATOR study

The NAVIGATOR trial was a phase one trial of avapritinib, and blu 285 in patients with unresectable or metastatic GIST. And the data that I presented at ESMO were basically two components of the phase one trial. The first was the efficacy data in patients with tumors harboring the PDGFR alpha D842V mutation, which is known to be a very resistant mutation to other tyrosine kinase inhibitors. That component consisted of 56 patients treated within the dose-escalation and dose-expansion, part of the navigator trial. And the second component was the safety analysis performed on all 250 patients with other types of mutations, both KIT and PDGFR alpha. And again, from both the dose-escalation and expansion cohort self, the phase one trial, and essentially the trial showed that avapritinib is very active in tumors with the PDGFR alpha D842V mutation.

So the objective response rates for all doses within the phase one trial was 91 percent. So 51 out of 56 patients had a response and the median duration of response with avapritinib at the 300 or 400-milligram dose was 22 months. The median progression-free survival was 24 months. The median overall survival was not reached, so very impressive efficacy data that have led to the FDA approval of avapritinib for GIST harboring the PDGFR alpha D842V mutation. In terms of the safety data from the NAVIGATOR trials for the entire safety population of 250 patients, who have a number of relatively common adverse events for tyrosine kinase inhibitors in nausea, anemia, diarrhea, fatigue, periorbital edema, but one of the things to note is the neurocognitive effects that can occur with this drug and for the safety population of 250 patients, any grade incidents of cognitive effects was 46 percent.

These included a number of effects, including memory impairment, confusional state cognitive disorder, and encephalopathy. And these are usually manageable with dose interruption or reduction. And in this trial, these interventions like dose interruption and reduction were effective in terms of improving grade two or greater cognitive adverse events in a median of 12 days. And the other adverse event to notes is intracranial bleeding. And again, in the safety population of 250 patients, this occurred in three patients, sorry, in 3 percent or seven patients. So the bottom line from this trial is that avapritinib is effective in metastatic or unresectable PDGFR alpha D842V mutation GIST this is a population of patients with a high unmet medical need. And of course, this has led to the approval of this agent by the FDA for this indication. And in terms of the safety profile, the drug is generally tolerable. And those similar safety profile between the entire cohorts of patients treated within the phase one trial and the patients with tumors harboring the D842V mutation.