On January 4th, 2018 Deciphera Pharmaceuticals, Inc, announced the start of the Phase 3 INVICTUS trial. This randomized trial is for 4th line GIST patients that have failed (or are intolerant) the three standard drugs for GIST, Gleevec, Sutent and Stivarga.
The press release can be found here.
Patients entering the trial will be randomized to DCC-2618 or placebo in a 2 to 1 ratio. Patients progressing on placebo will be allowed to crossover to receive DCC-2618. The primary endpoint of the trial will be progression-free survival. Patients with known wild-type GIST (e.g., SDH-deficient or mutation BRAF GIST) are not eligible for the trial.
DDC-2618 works at a different location in the KIT protein than typical kinase inhibitors. Instead of targeting the ATP binding pocket like most kinase inhibitors, DDC-2618 binds to the switch pocket. It blocks a much wider range of mutations, including the active conformation of the kinase, such as mutations in KIT exon 17 that cause secondary resistance and PDGFRA D842V mutations.
Dr. Filip Janku, of MD Anderson Cancer Center , Houston, TX, presented updated results of the phase I trial at the 2017 ESMO meeting in September (abstract 14730). In the phase I trial, doses from 40 to 400 mg either once or twice per day were tested. The dose selected for expansion phase was 150 mg per day.
Patients in the trial had received an average of 3.4 prior lines of therapy. FDG PET scans, CT scans and plasma cell-free DNA (cfDNA) were used to evaluate response. The majority of patients with KIT mutations showed a response; 22 of 32 (69%) had a partial metabolic response (PET) by EORTC criteria and 5 of 37 achieved partial response per RECIST criteria (significant shrinkage on CT scans). Disease-control rate (DCR) for patients receiving ≥100 mg per day was 76% at 12 weeks and 57% at 24 weeks. The median PFS time had not been reached as of July 28th, 2017. There was a marked reduction of cfDNA across all mutation types, and although based on small numbers and still preliminary, use of liquid biopsies appears favorable over tissue biopsies. The most common side effects were; lipase increase, fatigue, anemia, decreased appetite and diarrhea.
These results are quite encouraging. Participating countries for the phase 3 trial will include: USA, Canada, Belgium, Finland, France, Germany, Italy, Netherlands, Poland, Spain, UK, Australia and Singapore.
More information can be found on the LRG Clinical Trials Database.