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NCT04295759

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

Completed Phase 1 Results posted Last updated 5 January 2026
What this trial tests

Phase 1 trial testing INCB7839 in Glioblastoma Multiforme in 13 participants. Completed in 1 December 2024.

Timeline
27 July 2020
Primary endpoint
31 December 2023
1 December 2024

Quick facts

Lead sponsorPediatric Brain Tumor Consortium
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment13
Start date27 July 2020
Primary completion31 December 2023
Estimated completion1 December 2024
Sites11 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Pediatric Brain Tumor Consortium

Who can join

Adults 3 to 21, any sex, with Glioblastoma Multiforme or Anaplastic Astrocytoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Patients Who Experienced Dose-limiting Toxicities (DLTs) Primary · Approximately 28 days

All subjects evaluable for dose-finding were classified as having DLT or not having DLT, and the number of subjects having DLT was reported. Any INCB7839-related adverse events during the first course of treatment that led to dose reduction, permanent cessation of therapy, or a delay in treatment of \>7 days were considered DLTs. Hematologic DLTs included any grade 4 hematologic toxicity except lymphopenia; grade 3 neutropenia with fever; or requiring a platelet transfusion on 2 separate days during a single course. Non-hematologic DLTs included any grade 4 non-hematologic toxicity; any grade

GroupValue95% CI
Dose Level 1 (120 mg/m^2/Dose)3
Maximum Tolerated Dose (MTD) and/or Recommend Phase II Dose (RP2D) of INCB7839 Primary · Approximately 28 days

A design similar to the Rolling-6 design was used and 6 slots were initially opened on the starting dose level (dose level 1, INCB7839 120 mg/m\^2/dose BID). If no more than one dose-limiting toxicity (DLT) was observed in these 6 subjects, we would expand this cohort to at least 12 patients for additional safety and pharmacokinetic information. If more than 3 DLTs were observed in 12 subjects at dose level 1, then the initially identified maximum tolerated dose based on 6 subjects would be considered unsafe and de-escalation to a lower dose level (INCB7839 80 mg/m\^2/dose BID) would be consid

GroupValue95% CI
Dose Level 1 (120 mg/m^2/Dose)NA
Area Under the Curve (AUC) of INCB7839 Primary · Up to 3 days after the start of treatment

Pharmacokinetic (PK) studies were performed after an oral INCB7839 dose on days 1, 2, and 3 of Course 1. Beginning day 1 of Course 1, INCB7839 serial blood PK samples were drawn pre-dose and at approximately 1, 4, 8, 24, and 48 hours after the first dose. Time points at which data were collected to create the curve were 0, 1, 4, 8, 24 and 48 hours post-dose. The area under the curve (AUC) was estimated using a noncompartmental method.

GroupValue95% CI
Dose Level 1 (120 mg/m^2/Dose)38521820 – 8638
Maximum Concentration [Cmax] of INCB7839 Primary · Up to 3 days after the start of treatment

Pharmacokinetic (PK) studies were performed after an oral INCB7839 dose on days 1, 2, and 3 of Course 1. Beginning day 1 of Course 1, INCB7839 serial blood PK samples were drawn pre-dose and at approximately 1, 4, 8, 24, and 48 hours after the first dose. Time points at which data were collected were 0, 1, 4, 8, 24 and 48 hours post-dose. The maximum concentration (Cmax) was estimated using a noncompartmental method.

GroupValue95% CI
Dose Level 1 (120 mg/m^2/Dose)558130 – 1262
Apparent Oral Clearance [CL/F] of INCB7839 Primary · Up to 3 days after the start of treatment

Pharmacokinetic (PK) studies were performed after an oral INCB7839 dose on days 1, 2, and 3 of Course 1. Beginning day 1 of Course 1, INCB7839 serial blood PK samples were drawn pre-dose and at approximately 1, 4, 8, 24, and 48 hours after the first dose. Time points at which data were collected were 0, 1, 4, 8, 24 and 48 hours post-dose. Clearance (CL/F) was estimated using a noncompartmental method.

GroupValue95% CI
Dose Level 1 (120 mg/m^2/Dose)34.618.5 – 68.5
Time to Reach Maximum Concentration [Tmax] of INCB7839 Primary · Up to 3 days after the start of treatment

Pharmacokinetic (PK) studies were performed after an oral INCB7839 dose on days 1, 2, and 3 of Course 1. Beginning day 1 of Course 1, INCB7839 serial blood PK samples were drawn pre-dose and at approximately 1, 4, 8, 24, and 48 hours after the first dose. Time points at which data were collected were 0, 1, 4, 8, 24 and 48 hours post-dose. The time to reach maximum concentration (Tmax) was estimated using a noncompartmental method.

GroupValue95% CI
Dose Level 1 (120 mg/m^2/Dose)4.03.9 – 8.4
Percent Probability of Progression-free Survival Secondary · 3 months from first dose of INCB7839

Progression-free survival (PFS) was defined as the time interval from date of treatment start to date of first event (progressive disease or death due to any cause) for patients with events, or to the date of last follow-up for patients without events. PFS was estimated using the method of Kaplan and Meier and reported with a 95% confidence interval. We had planned to report the 2-year PFS estimate, but the 2-year estimate was not defined as most subjects progressed prior to 2 years. The 3-month PFS estimate was reported. All subjects are off study and data collection has concluded for this ou

GroupValue95% CI
Dose Level 1 (120 mg/m^2/Dose)18.180 – 40.97
Percent Probability of Overall Survival Secondary · 3 months from first dose of INCB7839

Overall survival (OS) was defined as the time interval from date of treatment initiation to date of death due to any cause or to the date of last follow-up for survivors. OS was estimated using the method of Kaplan and Meier and reported with a 95% confidence interval. All subjects are off study and data collection has concluded for this outcome measure.

GroupValue95% CI
Dose Level 1 (120 mg/m^2/Dose)53.6917.02 – 90.36
ADAM10 Inhibition of HER2 Secondary · Baseline and Day 14 of Course 1

HER2 extracellular domain (ECD) in serum will be reported.

Baseline
GroupValue95% CI
Dose Level 1 (120 mg/m^2/Dose)16.664.24 – 37.26
Course 1, Day 14
GroupValue95% CI
Dose Level 1 (120 mg/m^2/Dose)17.554.64 – 114.00

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dose Level 1 (120 mg/m^2/Dose)
Serious: 9/11 (82%)
Deaths: 4/11

Serious adverse events (28 terms)

ReactionSystemDose Level 1 (120 mg/m^2/D…
HydrocephalusNervous system disorders
VomitingGastrointestinal disorders
HeadacheNervous system disorders
SeizureNervous system disorders
SomnolenceNervous system disorders
AnemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
Death NOSGeneral disorders
Disease progressionGeneral disorders
FatigueGeneral disorders
Lung infectionInfections and infestations
SepsisInfections and infestations
ThrushInfections and infestations
Alanine aminotransferase increasedInvestigations
Lymphocyte count decreasedInvestigations
White blood cell decreasedInvestigations
HyperkalemiaMetabolism and nutrition disorders
AtaxiaNervous system disorders
Cerebral Venous ThrombosisNervous system disorders
Depressed level of consciousnessNervous system disorders
DysarthriaNervous system disorders
EncephalopathyNervous system disorders
Intracranial hemorrhageNervous system disorders
Paroxysmal Sympathetic HyperactivityNervous system disorders
Posterior Reversible Encephalopathy SyndromeNervous system disorders
Other adverse events (29 terms — click to expand)

ReactionSystemDose Level 1 (120 mg/m^2/D…
Alanine aminotransferase increasedInvestigations
Lymphocyte count decreasedInvestigations
FatigueGeneral disorders
HypoalbuminemiaMetabolism and nutrition disorders
Aspartate aminotransferase increasedInvestigations
Platelet count decreasedInvestigations
White blood cell decreasedInvestigations
AnemiaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
HypokalemiaMetabolism and nutrition disorders
HypophosphatemiaMetabolism and nutrition disorders
Hemoglobin increasedInvestigations
HyponatremiaMetabolism and nutrition disorders
HeadacheNervous system disorders
VertigoEar and labyrinth disorders
Dry eyeEye disorders
ConstipationGastrointestinal disorders
DiarrheaGastrointestinal disorders
VomitingGastrointestinal disorders
FeverGeneral disorders
AnorexiaMetabolism and nutrition disorders
HyperkalemiaMetabolism and nutrition disorders
HypocalcemiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
Generalized muscle weaknessMusculoskeletal and connective tissue disorders
SomnolenceNervous system disorders
Dry skinSkin and subcutaneous tissue disorders
Neutrophil count decreasedInvestigations
LeukocytosisBlood and lymphatic system disorders

Most-reported serious reactions: Hydrocephalus, Vomiting, Headache, Seizure, Somnolence, Anemia, Constipation, Death NOS.

Data from ClinicalTrials.gov NCT04295759 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Concepts of extracellular matrix remodelling in tumour progression and metastasis.
    Winkler J, Abisoye-Ogunniyan A, Metcalf KJ, Werb Z. · · 2020 · cited 1644× · PMID 33037194 · DOI 10.1038/s41467-020-18794-x
  2. Cancer neuroscience: State of the field, emerging directions.
    Winkler F, Venkatesh HS, Amit M, Batchelor T, et al · · 2023 · cited 357× · PMID 37059069 · DOI 10.1016/j.cell.2023.02.002
  3. The neuroscience of cancer.
    Mancusi R, Monje M. · · 2023 · cited 244× · PMID 37316719 · DOI 10.1038/s41586-023-05968-y
  4. Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.
    Shi Q, Xue C, Zeng Y, Yuan X, et al · · 2024 · cited 242× · PMID 38797752 · DOI 10.1038/s41392-024-01828-x
  5. The Notch signaling pathway: a potential target for cancer immunotherapy.
    Li X, Yan X, Wang Y, Kaur B, et al · · 2023 · cited 114× · PMID 37131214 · DOI 10.1186/s13045-023-01439-z
  6. Therapeutic avenues for cancer neuroscience: translational frontiers and clinical opportunities.
    Shi DD, Guo JA, Hoffman HI, Su J, et al · · 2022 · cited 104× · PMID 35114133 · DOI 10.1016/s1470-2045(21)00596-9
  7. Circadian Rhythms and Astrocytes: The Good, the Bad, and the Ugly.
    Hastings MH, Brancaccio M, Gonzalez-Aponte MF, Herzog ED. · · 2023 · cited 47× · PMID 36854316 · DOI 10.1146/annurev-neuro-100322-112249
  8. Challenges and Recent Advances in NK Cell-Targeted Immunotherapies in Solid Tumors.
    Lian G, Mak TS, Yu X, Lan HY. · · 2021 · cited 44× · PMID 35008589 · DOI 10.3390/ijms23010164

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Other recruiting trials for Glioblastoma Multiforme

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