CTOS 2023 – IDRx looks to outdo Deciphera

KIT inhibition has proven a money spinner for the likes of Deciphera and Blueprint Medicines, and now a new contender, IDRx, reckons it can outdo its rivals. Early data presented last week at the Connective Tissue Oncology Society (CTOS) meeting suggest that IDRX-42 might have the edge over Deciphera’s Qinlock in late-line gastrointestinal stromal tumours.

And privately held IDRx reckons that there could be more to come with IDRX-42, which it claims can hit all major classes of primary drivers and resistance mutations in patients with KIT-mutant GIST.

The phase 1 Strategist study of IDRX-42 enrolled heavily pretreated GIST patients, with a median four prior lines of therapy and with various KIT mutations. Given that Qinlock is approved in fourth-line or later GIST, the Deciphera drug's registrational Invictus trial thus looks like the most relevant comparator.

Strategist, which tested escalating doses of IDRX-42, found a 14% overall response rate, with four partial responses among 28 evaluable patients. Invictus, meanwhile, posted a 9% response rate among 85 Qinlock-treated patients, versus 0% with placebo.

Room for improvement?

Cross-trial comparisons should always be undertaken with caution, particularly given the small number of patients receiving IDRX-42. However, IDRx’s chief executive, Ben Auspitz believes that the response rate with the project could improve.

He noted that Strategist hadn't yet found a maximally tolerated dose of IDRX-42, and that median time to response in GIST could be five to six cycles; patients in Strategist have received two cycles so far.

And, notably, around 40% of patients in Strategist had already been treated with Qinlock, with one partial response seen in this population, Auspitz told ApexOnco.

With tolerability looking acceptable at doses of up to 600mg daily, IRDx is pushing to a 400mg twice-daily dose, and ultimately hopes to move IDRX-42 into earlier lines of therapy.

Here, the asset could go up against Qinlock again. Although the Deciphera drug is not approved beyond fourth-line GIST, the company is seeing increased off-label use in second-line disease, it said during its recent third-quarter conference call.

Meanwhile, IDRX-42 is not an immediate threat to Blueprint’s KIT and PDGFRA inhibitor Ayvakit, which is approved for a GIST niche, patients with PDGFRA exon 18 mutations. These patients were excluded from Strategist. This shouldn't hurt IDRX-42’s commercial prospects if the IDRx project successfully navigate the long path to market: 80-90% of GIST is driven by KIT mutations, IDRx estimates.