Dr. Vinayak Venkataraman, medical oncologist and director of Sarcoma Pathways at Dana-Farber Most cancers Institute in Boston, lately sat down with CURE to debate the evolving therapy panorama for gastrointestinal stromal tumors (GIST).
An teacher in drugs and affiliated college on the McGraw/Patterson Heart for Inhabitants Sciences, Harvard Medical Faculty, Venkataraman shared insights on rising second- and third-line therapies, notable investigational brokers in growth, and novel approaches for underserved affected person populations.
CURE: Might you spotlight any ongoing or latest scientific trials in GIST that you’re significantly enthusiastic about?
Venkataraman: Sure! There are two trials that I feel are most likely probably the most enthusiastic about. One among them is named the PEAK trial, and it was a part 3 trial trying on the mixture of Sutent (sunitinib) plus one other KIT inhibitor referred to as bezuclastinib (CGT9486), and evaluating that to Sutent in predominantly the second line of therapy.
Most sufferers who’re identified with GIST will all be handled with Gleevec (imatinib) because the first-line therapy. However oftentimes, often, on common, two years after beginning therapy, their GIST develops resistance to the Gleevec, and Sutent is conventionally the second-line therapy in that inhabitants. This trial was taking a look at, “Can we do higher than [Sutent] within the second line?”
We’re hoping to get a readout of that trial very quickly. … I think about, if not on the ESMO Congress, it could be introduced on the 2026 ASCO Annual Assembly this upcoming 12 months. That’s thrilling as a result of that might be a possible second-line therapy.
There’s one other novel compound referred to as IDRX-42 which was examined in a closely pretreated inhabitants, together with within the second line, the place it had a really encouraging goal response price in that closely pretreated inhabitants and nearly a 50% response price within the second line. That was introduced at our Connective Tissue Oncology Society assembly final 12 months in San Diego, and based mostly on these outcomes of how effectively sufferers have been doing on the second line, we’ll be half of a giant multicenter trial taking a look at Sutent versus IDRX-42 in that second-line inhabitants.
Once more, these are two potential novel compounds or novel mixtures that would doubtlessly change our commonplace of care within the second and third line of therapy. So these are those we’re most enthusiastic about.
Moreover, there are some part 1 trials trying on the mixture of Gleevec and a menin inhibitor, as a result of biologically within the lab, there’s been some synergy seen in sufferers who’ve progressed on Gleevec by itself. Moreover, then are some pan-KIT inhibitors popping out which might be additionally in scientific trial.
Are you able to clarify how analysis is approaching therapy for underserved affected person populations with GIST and whether or not there are any focused therapies being investigated for affected person subgroups?
Lastly, as I discussed, most gastrointestinal stromal tumors are pushed by mutations in KIT and PDGFR, however in 10% to fifteen% of instances, these proteins aren’t impacted. A typical kind that we see in younger adults is named SDH-deficient gastrointestinal stromal tumor, or SDH-deficient GIST. There’s curiosity in [this topic], and we hope to launch a trial taking a look at, an FGFR inhibitor, as a result of biologically, within the lab, it has been seen that that appears to be a vulnerability. If you happen to block the FGFR receptor in sufferers with SDH-deficient GIST, there does appear to be some anti-cancer impact.
Beforehand, there was an FGFR inhibitor referred to as regorafenib that did have some encouraging preliminary outcomes however wasn’t taken ahead by the corporate sponsor. So, the hope is that with this totally different FGFR inhibitor, we’ll see some extra encouraging outcomes.
Transcript has been edited for readability and conciseness.
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