GSK prepares its kit in GIST

GSK is moving its KIT inhibitor, IDRX-42 (GSK6042981), into a pivotal trial, nearly a year after the project’s originator IDRx reached an agreement with the FDA on the trial’s design, dose, and statistical analysis. 

According to a new clinicaltrials.gov listing, the phase 3 Strategist-3 study will evaluate GSK6042981 against Sutent in second-line gastrointestinal stromal tumour (GIST) patients, with PFS as the primary endpoint.

The move marks a major step for the programme, which GSK picked up through its $1bn acquisition of IDRx in January. The deal came shortly after IDRx reported encouraging results from the phase 1 Strategist-1 trial, where IDRX-42 demonstrated a 20% ORR among 10 heavily pretreated, fourth-line or later, GIST patients. Median PFS reached 11.0 months.

Perhaps more relevant to Strategist-3, there was a 46% ORR in 13 second-line patients treated at the recommended dose of 300mg in tablet formulation, or 400mg in capsule formulation.

Overall, grade 3/4 adverse events occurred in 24% of patients, while 2% discontinued, though none at the recommended dose.

For context, Sutent, the current standard in this setting, has historically achieved around 18% ORR, so this is the bar that GSK6042981 will likely need to beat in Strategist-3.

Also in second-line GIST, Cogent Biosciences is expected to deliver data with bezuclastinib in combination with Sutent, versus Sutent alone, from its phase 3 Peak trial in November. In the lead-in portion of this study, Cogent reported a 33% ORR and a median PFS of 19.4 months in a subset of second-line GIST patients with only prior Gleevec which, Cogent said, most closely resembles patients enrolling in Part 2 of Peak. 

Another KIT inhibitor rival is Qinlock, originally developed by Deciphera, which Ono Pharmaceutical acquired in 2024 for $2.4bn. Qinlock is approved for fourth-line GIST, but flunked the second-line Intrigue study, and it’s now in the phase 3 Insight trial, which is limited to second-line patients harbouring KIT exon 11 and 17/18 mutations.

Strategist-1 also contains a cohort of patients with treatment-naive GIST, perhaps providing a clue to where GSK might take this project next.