You have to be very strategic as a patient when entering a phase I trial, which is a dose escalation study. There’s a risk of getting a dose which is below the therapeutic level if you enter the trial during its early recruitment. And there’s a risk of getting a high toxic dose if you enter late in the recruitment. In other words, a phase I trial may not be giving you the right dose of the drug because no one has yet determined what that dose should be. It’s like merging into traffic, you have to merge into the trial at a time when their dose escalation is near the “right dose”.
You want to know from your doctor where they are in the dose escalation and whether anyone with exon 9 mutant KIT GIST has shown a response in trial. You want to know this because you are weighing against the option of Sutent. Many if not most phase I study patients are out of options and so they have nothing to lose. But when Sutent has not yet been tried, there is theoretically something to lose.
Deciphera’s press release about its phase I DCC–2618 data presented at ASCO.
The drug had a 60% disease control rate at 24 weeks across the spectrum of KIT exon mutations. Sounds like phase III trials are being planned.
Results from the completed dose escalation stage of the ongoing Phase 1 study in 38 heavily pretreated patients with KIT or PDGFRα driven GIST as of May 8, 2017 were presented on June 5 at the American Society of Clinical Oncology (ASCO) Annual Meeting 2017, in Chicago, IL. Highlights of the poster presentation include:
At doses of 100 mg or greater daily, DCC–2618 produced a disease control rate (DCR) of 78% at 12 weeks (n=23) and a DCR of 60% at 24 weeks (n= 15) in GIST patients with KIT and PDGFRα driven disease. DCR is defined as patients with stable disease or partial response as assessed by Response Evaluation Criteria in Solid Tumors, or RECIST.
A dose of 150 mg once per day has been selected for the expansion cohorts and planned Phase 3 pivotal trials.
Compared to baseline values for cfDNA KIT mutant allele frequencies (MAF), extensive reductions were observed with DCC–2618, demonstrating pan-KIT activity across the spectrum of exons 9, 11, 13, 14, 17 and 18 mutations at starting doses as low as 30 mg BID.
DCC–2618 was generally well tolerated at all dose levels studied with no discontinuations due to a lack of tolerability or toxicity.
A durable partial response of more than 18 months in one glioblastoma patient dosed at 20 mg twice per day (94% tumor reduction) as assessed by Revised Assessment in Neuro-Oncology or RANO was noted.
DCC 2618 inhibits KIT by a completely novel mechanism. DCC 2618 binds to an area of KIT called the “switch pocket” rather than in the “catalytic pocket” which is where Gleevec, Sutent, Stivarga, Tasigna, Votrient, Iclusig, BLU285 and all other KIT targeting drugs bind. So what is the “switch pocket” ?? Deciphera answered this question for us a few years ago:
https://www.gistsupport.org/
DCC 2618 also inhibits VEGFR2. From the trial protocol it inhibits:
“KIT, PDGFR (A or B), TIE2, CSF1R, and VEGFR2”