Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioma

Glioblastoma

Astrocytoma

Oligodendroglioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Neuroepithelioma

INCB7839 dosing will begin at 120 mg/m2/dose BID which is equivalent to the adult RP2D (200 mg PO BID) based on a typical adult size of 1.67m2. The INCB7839 dose may be decreased to 80 mg/m2/dose BID if the staring dose is not tolerable. 28 consecutive days (4 weeks) will constitute one course. Patients may continue to receive INCB7839 for 26 courses (approximately 2 years).

INCB7839

Michelle Monje, MD, PhD

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.

This is a phase I study and we will use a design similar to the Rolling-6 design and open 6 slots initially on Dose level 1. If we observe no-more than 1 DLT in these 6 subjects then we would expand this cohort to at least 12 patients for PK and additional safety information. If more than 1 DLT is observed on dose level 1 in 2-6 subjects, then further enrollment to dose level 1 will stop, the dose will be de-escalated to dose level 0 and the same approach will be repeated. Based on the above-outlined de-escalation rules, if dose level 0 is found to be too toxic, then the trial will be closed to accrual and the merits of amending or closing the trial permanently will be reconsidered.

INCB7839 in Treating Children With Recurrent/Progressive High-Grade Gliomas

A Phase I Study of the Adam-10 Inhibitor, INCB7839 in Children With Recurrent/Progressive High-Grade Gliomas to Target Microenvironmental Neuroligin-3

HER2 extracellular domain in serum will be reported.

Neuroligin-3 (NLGN3) in cerebral spinal fluid will be reported.

The maximum concentration \[CMAX\] will be calculated based on the CSF pharmacokinetic samples.

Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0.

To estimate the maximum tolerated dose (MTD) and/or recommend Phase II dose (RP2D) of INCB7839 administered orally in children with recurrent/progressive high-grade glioma.

The area under the curve (AUC) will be calculated based on the course 1 days 1 and 2 pharmacokinetic samples.

The maximum concentration \[CMAX\] will be calculated based on the course 1 days 1 and 2 pharmacokinetic samples.

The apparent oral clearance \[CL/F\] will be calculated based on the course 1 days 1 and 2 pharmacokinetic samples.

The time to reach CMAX \[TMAX\] will be calculated based on the course 1 days 1 and 2 pharmacokinetic samples.

The progression-free survival will be reported.

The duration of response will be reported.

National Cancer Institute (NCI)

American Lebanese Syrian Associated Charities (ALSAC)

Pediatric Brain Tumor Consortium

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

B-cell Lymphoma

Lymphosarcoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Rituximab

Antineoplastic Agents, Immunological

Immunologic Factors

Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab

Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later

INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab

Veronika Bachanova, MD

This is a single institution phase I/II study using an ADAM17 inhibitor (INCB7839) with rituximab as consolidation therapy after an autologous hematopoietic cell transplant (HCT) for patients with diffuse large B cell lymphoma (DLBCL). The study consists of two phases. The dose finding phase is a modified version of a phase I trial and the extended phase is a modified version of a phase II trial.

The primary goal of the dose finding phase is to determine the maximum tolerated dose (MTD) of INCB7839. Up to three dose levels will be tested (100 mg bid, 200 mg bid, and 300 mg bid). As the 300 mg bid has been proven safe in the non-transplant setting, dose escalation follows a Fast-Track Design with 1 patient enrolled per dose level unless a grade 2 or greater treatment emergent event occurs within the 1st 14 days of INCB7839. At that point, dose escalation converts to a standard 3+3 design and two additional patients are enrolled at the current dose level. If dose level 3 is completed without dose limiting toxicity (DLT) in the 1st 3 patients, an additional 3 patients will be enrolled at this level (without the staggering required by the DLT rules) prior to moving to the phase II component.

Once the phase I dose escalation is completed, an additional 12 patients will be enrolled at the MTD (or dose level 3, if no DLT) to obtain a more detailed toxicity profile as well as a preliminary estimate of progression free survival at 6 months post-transplant.

A Fast-Track Design with 1 patient enrolled per dose level until a grade 2 or greater treatment emergent adverse event occurs. A treatment emergent adverse event is any event not present prior to the initiation of the treatment (INCB7839) or any event already present that worsens in either intensity or frequency following exposure to the treatment. At that point, dose escalation will convert to a standard 3+3 design with two additional patients enrolled at the same dose level. If dose level 3 is completed without dose limiting toxicity (DLT) in the 1st 3 patients, an additional 3 patients will be enrolled at this level (without the staggering required by the DLT rules) prior to moving to the phase II component.

Once the phase I dose escalation is completed, an additional 12 patients will be enrolled at the MTD (or dose level 300mg bid, if no DLT) to obtain a more detailed toxicity profile as well as a preliminary estimate of progression free survival at 6 months post-transplant.

ADAM17 Inhibitor/ Rituximab After Auto HCT for DLBCL

Study of the ADAM17 Inhibitor INCB7839 Combined With Rituximab After Autologous Hematopoietic Cell Transplantation (HCT) For Patients With Diffuse Large B Cell Non-Hodgkin Lymphoma (DLBCL)

The Phase I design will continue until the MTD is declared or until the first dose is declared to be above MTD. Phase I dose limiting toxicity (DLT) is defined as Grade 3-5 non-hematologic, non-infectious toxicity including thromboembolic complications and select hematologic events including: grade 4 neutropenia lasting for ≥ 7 days, febrile neutropenia, grade 4 thrombocytopenia lasting ≥ 7 days despite dose delay or grade 3 thrombocytopenia associated with bleeding.

This primary end point will be estimated with Kaplan-Meier curves.

To determine incidence of serious adverse events

Masonic Cancer Center, University of Minnesota

Rituximab will be given after day +28 re-staging and again 1 and 7 weeks later, followed by INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab

Rituximab: Rituximab 375 mg/m2 IV after day +28 (as late as day 75) re-staging and again 1 and 7 weeks later

INCB7839: INCB7839 at assigned dose twice daily for 90 days - begin the morning of the 2nd dose of rituximab

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
INCB7839 in Treating Children With Recurrent/Progressive High-Grade Gliomas	NCT04295759	Glioblastoma Mu... Anaplastic Astr... Anaplastic Olig... DIPG High-grade Astr... CNS Primary Tum...	INCB7839	3 Years - 21 Years	Pediatric Brain Tumor Consortium
ADAM17 Inhibitor/ Rituximab After Auto HCT for DLBCL	NCT02141451	Diffuse Large B...	Rituximab INCB7839	18 Years -	Masonic Cancer Center, University of Minnesota

Spots Global Cancer Trial Database for incb7839

Every month we try and update this database with for incb7839 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for incb7839

Every month we try and update this database with for incb7839 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for incb7839 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.