GSK continues to accelerate the development of velzatinib, the KIT inhibitor it acquired via IDRx: the phase 3 Strategist-Frontline study in newly diagnosed gastrointestinal stromal tumours (GIST) has just been listed on clinicaltrials.gov.
Here, the company is ahead of its KIT rival Cogent, which is set to begin a phase 2 first-line study this half with its contender, bezuclastinib. Both groups will have data at ASCO – and the results of a velzatinib trial in first-line GIST will be reported for the first time.
These come from the phase 1 Strategist-1 study, which has previously yielded later-line data. The ASCO abstract, released on Thursday evening, disclosed a 61% response rate among 18 front-line patients; however, all of these are unconfirmed as of the cutoff date of 15 December 2025.
This number will need to hold up to justify GSK’s decision to push into Strategist-Frontline, due to start in June. The trial will compare velzatinib against Novartis’s tyrosine kinase inhibitor Gleevec, with a primary endpoint of overall survival. GSK previously disclosed plans to start the study in the second half of this year, so it appears to be slightly ahead of schedule.
Front-line benchmark
However, the bar that velzatinib needs to hit is unclear. Gleevec received accelerated approval for GIST back in 2002, and a phase 2 trial published that year cites a 53% overall response rate; however, as well as being nearly 25 years old, that study also included patients who had previously received chemotherapy.
More recently, a combination of Gleevec and Pfizer’s MEK inhibitor Mektovi have shown promise in first-line GIST in an investigator-sponsored trial, but this regimen doesn’t appear to be being developed by either company.
Nevertheless, front-line GIST looks like a field that’s ripe for improved therapies, and GSK will hope to show a benefit with velzatinib. The UK group, which gained velzatinib through the $1bn takeout of IDRx in January 2025, already has a second-line pivotal trial under way, Strategist-3, comparing velzatinib against Sutent in post-Gleevec patients.
Bezuclastinib Peak
The bar here has been set by Cogent, which already filed a bezuclastinib/Sutent combo with the FDA in April, based on the Peak study in the post-Gleevec setting. The group hasn’t yet disclosed the agency’s acceptance or a PDUFA date.
Peak will also feature at ASCO, although the results outlined in the abstract look identical to those toplined in November, with bezuclastinib/Sutent reducing the risk of progression or death by 50% versus Sutent alone.
Cogent is also planning a filing soon for bezuclastinib in advanced systemic mastocytosis, and is awaiting an FDA decision in non-advanced systemic mastocytosis by 30 December. Here, it could compete with Sanofi’s Ayvakit, gained via that company's purchase of Blueprint.
So far, GSK hasn’t made any move to study velzatinib in mastocytosis.
Ayvakit is also approved in GIST, but only in patients with PDGFRA exon 18 mutations. Another GIST player player is Ono, whose Deciphera-originated Qinlock is marketed for fourth-line GIST.
Rival KIT inhibitors in GIST
| | Velzatinib (GSK) | Bezuclastinib (Cogent) |
|---|
| 1st-line | Ph3 Strategist-Frontline, monoRx vs Gleevec, to start Jun 2026 | Ph2 to start in H1, + Sutent in pts with exon 9 mutations who are naive to, or recently started on, Gleevec |
| 2nd-line | Ph3 Strategist-3, monoRx vs Sutent, completes May 2038 | Ph3 Peak, + Sutent vs Sutent, filed with FDA Apr 2026 |
