Gastrointestinal Tumor (GIST) is a type of soft tissue sarcoma found in the digestive (gastrointestinal, GI) tract. It is most common in people between the age of 50 and 70, with a median age of 58 years. GIST mostly occurs in stomach (about 50%), small bowel (about 25%), and in colon and rectum (about 10%). Around 70 to 80% of GISTs are benign, while 20 to 30% are malignant.
GISTs are defined by activating mutations in the KIT or PDGFRA genes. KIT mutations are found in 80-85% of GISTs, and PDGFRA mutations are found in 5-10% of GIST. These mutations are mutually exclusive (i.e., there are no reported cases of both KIT and PDGFRα mutations in the same tumor).
The most common PDGFRα mutation in GIST (62.5%) is an aspartic acid to valine substitution mutation at position 842 (D842V) that renders the tyrosine kinase constitutionally active.
Although two different kinase inhibitors (imatinib and sunitinib) have now been FDA-approved for treatment of GIST, neither of these show clinical or in vitro activity against the D842V mutation.
No treatment options exist for this subset of GISTs outside of surgical resection.
Preclinical studies have shown crenolanib to be active in inhibiting downstream signaling of PDGFRα with the D842V mutation
Phase II Trial in GIST PDGFRA D842V
AROG Pharmaceuticals is conducting a Phase-II trial to investigate the clinical efficacy of crenolanib in GIST patients with the D842V mutation.
Key Inclusion Criteria:
Trial is ongoing at:
The current status of the ongoing trial is summarized below: