This is a multicenter phase 1 trial of INCB7839 for children with recurrent or progressive
high-grade gliomas, including, but not limited to, diffuse intrinsic pontine glioma (DIPG)
and other diffuse midline gliomas (DMGs), after upfront therapy.
INCB7839 is an inhibitor of the ADAM (A Disintegrin and Metalloprotease) 10 and 17 proteases.
Neuronal activity regulates glioma growth through neuroligin-3 (NLGN3). ADAM 10 is the
protease responsible for NLGN3 release into the tumor microenvironment and represents a
promising therapeutic target.
Pre-clinical studies of INCB7839 in patient-derived pediatric high-grade gliomas (GBM and
DIPG) revealed that INCB7839 inhibits pediatric high- grade glioma growth and improves
overall survival. In vivo testing also demonstrated that INCB7839 penetrates brain tissue
sufficient to achieve its pharmacodynamic effect of ADAM10 inhibition. Further pre-clinical
studies in other animals revealed minimal toxicity, including non-adverse to mild increases
in serum hepatobiliary enzymes, protein, calcium, cholesterol values, along with minimal
decreases in RBC mass parameters; all parameters recovered.
INCB7839 has been evaluated in Phase I and Phase II clinical trials for previously treated
solid tumors and breast cancer. Of the adverse events (AEs) noted, the majority were
mild-to-moderate in severity, the most frequent being fatigue, nausea, anorexia, diarrhea,
emesis, abdominal pain, anemia and constipation. The dose-limiting toxicity for monotherapy
with INCB7839 in Phase I clinical trials was declared to be deep venous thrombosis (DVT). Out
of 41 patients, there was a total of 9 thrombotic events including mild superficial
thrombophlebitis (n=1), DVT (n=4), vena cava thrombosis with renal insufficiency in a patient
with squamous cell cancer of the head and neck (n=1), atrial thrombosis in patient with
breast cancer (n=1), and pulmonary embolism in patients with hormone-refractory prostate
cancer (n=2). Overall, INCB7839 does exhibit a pro-coagulant effect in some adult patients,
resulting in an increased incidence of DVT, whether used alone or in combination. The
mechanism of this effect is unknown, and there is no clear relationship between the frequency
of thrombosis and the dose administered.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.