Gastrointestinal Tumor (GIST)

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.


Life Raft Group
GIST Support Internationaln

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:

  • ECOG PS ≤ 1
  • History of GIST with a documented PDGRA D842V mutation
  • Multiple prior relapses permitted

Trial is ongoing at:

  • Fox Chase Cancer Center
  • Oregon Health and Science University

Clinical Trial Number: NCT01243346

The current status of the ongoing trial is summarized below:

  • Absorption of crenolanib does not appear to be affected by gastrectomy.
  • Toxicities have mirrored phase I experience, with nausea and vomiting managed with daily ondansetron administration.
  • Preliminary metabolic response was observed in one patient.
  • Accrual into this trial is ongoing.