Dive Brief:
- Blueprint Medicines released fresh data Thursday from an ongoing Phase 1 clinical trial testing its drug avapritinib as a therapy for certain gastrointestinal tumors.
- Results from the registration-enabling NAVIGATOR clinical trial showed activity across all lines of therapy for patients with PDGFRα D842V-driven gastrointestinal stromal tumors (GIST) and in second-, third- and fourth-line for other GIST patients.
- The biotech plans to submit its first New Drug Application in the first half of 2019 for avapritinib, a selective KIT and PDGFRA inhibitor, for the treatment of PDGFRA exon 18 mutant GIST, and fourth-line GIST.
Dive Insight:
The updated NAVIGATOR trial results showed an 84% objective response rate (ORR) and a 76% 12-month duration of response (DoR) in patients with a mutation-driven form of GIST.
In patients with heavily pre-treated GIST, a difficult disease to tackle, the ORR was 20% and the median DoR was 7.3 months.
GIST is a rare cancer, and there are currently no effective therapies for patients with PDGFRα D842V-driven GIST and fourth-line disease.
Investors had a less-than-enthusiastic reaction to the update, sending shares down nearly 7% to $52.26 apiece by market's close Thursday. Shares ticked back up to over $53 apiece in late Friday morning trading, however.
Leerink analyst Andrew Berens described the responses in patients with the mutation-driven subtype and the fourth-line as "impressive" in a note. Berens predicts an accelerated approval for the drug in GIST in the first half of 2019 for patients in these subgroups.
"Importantly, all of these data have been centrally reviewed. The data in both settings compare favorably to current treatment paradigms and the durability and size of the datasets is encouraging," Berens wrote.
Data from the NAVIGATOR study could also be used to support future development for avapritinib in early lines of treatment, including second- and third-line therapy. The second-line data was strong with a 25% ORR — which comes out above the expected performance of Pfizer's Sutent (sunitinib), used as standard-of-care, and on par with Deciphera Pharmaceuticals' DCC-2618. Avapritinib is also in pivotal trials in fourth-line treatment.
"Given its unmatched activity in PDGFRα D842V, in addition to systemic mastocytosis, and now competitive profile in 2L patients, avapritinib is developing what appears to be a best in class profile for selective KIT/PDGFRα inhibitors," Berens wrote.
The next step is the second-line study, dubbed COMPASS-2L, which will exclude patients with the Gleevec resistance mutations V654A and T670I ( who represent around a quarter of the GIST population). The Deciphera second-line INTRIGUE study, scheduled to begin before year's end, will look at a broader population and compare DCC-2618 with Sutent.
"The data today suggest that the COMPASS-2L trial is likely to produce compelling results that would justify genetic profiling. We also believe there is the possibility that the drug will continue to be active in broader patients," Berens wrote.
Correction: A previous version of this story incorrectly reported the overall response rate for second-line data.