Trial Outcomes & Findings for INCB7839 in Treating Children With Recurrent/Progressive High-Grade Gliomas (NCT NCT04295759)

Last Updated: 2026-01-05

Results Overview

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 3 non-hematologic toxicities with some exceptions such as grade 3 fever or infection of fewer than 5 days in duration; any grade 2 non-hematologic toxicity persisting for \>7 days and considered medically significant; and any deep venous thrombotic event (superficial phlebitis was excluded unless grade 3 or 4 or unless it met another criteria for DLT).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

13 participants

Primary outcome timeframe

Approximately 28 days

Results posted on

2026-01-05

Participant Flow

Patients ≥3 and ≤21 years of age with recurrent or progressive high-grade gliomas including but not limited to diffuse intrinsic pontine glioma (DIPG) and other diffuse high-grade gliomas were enrolled at Pediatric Brain Tumor Consortium (PBTC) member institutions. The first patient was enrolled on 7/27/2020 and the last patient was enrolled on 2/7/2023. Only one dose level was studied; all subjects were enrolled on Dose Level 1 (120 mg/m\^2/dose).

Participant milestones

Participant milestones
Measure	Dose Level 1 (120 mg/m^2/Dose) Subjects with recurrent or progressive high-grade gliomas received 120 mg/m\^2/dose of INCB7839 orally, twice a day for 28-day cycles. Treatment could continue for up to 26 courses (approximately 2 years) in the absence of disease progression or unacceptable toxicity or another off treatment or off study reason.
Overall Study STARTED	13
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Level 1 (120 mg/m^2/Dose) Subjects with recurrent or progressive high-grade gliomas received 120 mg/m\^2/dose of INCB7839 orally, twice a day for 28-day cycles. Treatment could continue for up to 26 courses (approximately 2 years) in the absence of disease progression or unacceptable toxicity or another off treatment or off study reason.
Overall Study Lack of Efficacy	9
Overall Study Death	1
Overall Study Withdrawal by Subject	2
Overall Study Deemed ineligible	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level 1 (120 mg/m^2/Dose) n=12 Participants Subjects with recurrent or progressive high-grade gliomas received 120 mg/m\^2/dose of INCB7839 orally, twice a day for 28-day cycles. Treatment could continue for up to 26 courses (approximately 2 years) in the absence of disease progression or unacceptable toxicity or another off treatment or off study reason.
Age, Continuous	14.5 years n=9667 Participants
Sex: Female, Male Female	8 Participants n=9667 Participants
Sex: Female, Male Male	4 Participants n=9667 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=9667 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=9667 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=9667 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=9667 Participants
Race (NIH/OMB) Asian	0 Participants n=9667 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=9667 Participants
Race (NIH/OMB) Black or African American	2 Participants n=9667 Participants
Race (NIH/OMB) White	6 Participants n=9667 Participants
Race (NIH/OMB) More than one race	0 Participants n=9667 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=9667 Participants
Region of Enrollment United States	12 participants n=9667 Participants

PRIMARY outcome

Timeframe: Approximately 28 days

Population: Only eligible subjects and those evaluable for estimating the maximum tolerated dose (MTD) were included in this analysis (n=10). Of 13 subjects enrolled, 1 was deemed ineligible, and 2 were not evaluable for dose-finding as they received less than 85% of planned INCB7839 dosing during the dose-finding period for reasons other than toxicity, including 1 subject who withdrew prior to beginning therapy.

Outcome measures

Outcome measures
Measure	Dose Level 1 (120 mg/m^2/Dose) n=10 Participants Subjects with recurrent or progressive high-grade gliomas received 120 mg/m\^2/dose of INCB7839 orally, twice a day for 28-day cycles. Treatment could continue for up to 26 courses (approximately 2 years) in the absence of disease progression or unacceptable toxicity or another off treatment or off study reason.
Number of Patients Who Experienced Dose-limiting Toxicities (DLTs)	3 Participants

PRIMARY outcome

Timeframe: Approximately 28 days

Population: Of 13 subjects enrolled, 1 was deemed ineligible, and 2 were not evaluable for dose-finding as they received less than 85% of planned INCB7839 dosing during the dose-finding period for reasons other than toxicity, including 1 subject who withdrew prior to beginning therapy. Because we had 10 eligible, evaluable subjects rather than the required 12 needed to address this objective, we were unable to define the MTD and no result is reported.

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 considered.

Outcome measures

Outcome measures
Measure	Dose Level 1 (120 mg/m^2/Dose) n=10 Participants Subjects with recurrent or progressive high-grade gliomas received 120 mg/m\^2/dose of INCB7839 orally, twice a day for 28-day cycles. Treatment could continue for up to 26 courses (approximately 2 years) in the absence of disease progression or unacceptable toxicity or another off treatment or off study reason.
Maximum Tolerated Dose (MTD) and/or Recommend Phase II Dose (RP2D) of INCB7839	NA mg/m^2/dose Because we had 10 eligible, evaluable subjects rather than the required 12 needed to address this objective, we were unable to define the MTD and no result is available or reported for this outcome measure.

PRIMARY outcome

Timeframe: Up to 3 days after the start of treatment

Population: Eligible patients who had PK samples collected and had AUC data available were included in this analysis.

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.

Outcome measures

Outcome measures
Measure	Dose Level 1 (120 mg/m^2/Dose) n=11 Participants Subjects with recurrent or progressive high-grade gliomas received 120 mg/m\^2/dose of INCB7839 orally, twice a day for 28-day cycles. Treatment could continue for up to 26 courses (approximately 2 years) in the absence of disease progression or unacceptable toxicity or another off treatment or off study reason.
Area Under the Curve (AUC) of INCB7839	3852 h*ng/ml Interval 1820.0 to 8638.0

PRIMARY outcome

Timeframe: Up to 3 days after the start of treatment

Population: Eligible patients who had PK samples collected and who had Cmax data available were included.

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.

Outcome measures

Outcome measures
Measure	Dose Level 1 (120 mg/m^2/Dose) n=11 Participants Subjects with recurrent or progressive high-grade gliomas received 120 mg/m\^2/dose of INCB7839 orally, twice a day for 28-day cycles. Treatment could continue for up to 26 courses (approximately 2 years) in the absence of disease progression or unacceptable toxicity or another off treatment or off study reason.
Maximum Concentration [Cmax] of INCB7839	558 ng/ml Interval 130.0 to 1262.0

PRIMARY outcome

Timeframe: Up to 3 days after the start of treatment

Population: Eligible patients who had PK samples collected and who had CL/F data available were included.

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.

Outcome measures

Outcome measures
Measure	Dose Level 1 (120 mg/m^2/Dose) n=11 Participants Subjects with recurrent or progressive high-grade gliomas received 120 mg/m\^2/dose of INCB7839 orally, twice a day for 28-day cycles. Treatment could continue for up to 26 courses (approximately 2 years) in the absence of disease progression or unacceptable toxicity or another off treatment or off study reason.
Apparent Oral Clearance [CL/F] of INCB7839	34.6 L/hr/m^2 Interval 18.5 to 68.5

PRIMARY outcome

Timeframe: Up to 3 days after the start of treatment

Population: Eligible patients who had PK samples collected and who had Tmax data available were included.

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.

Outcome measures

Outcome measures
Measure	Dose Level 1 (120 mg/m^2/Dose) n=11 Participants Subjects with recurrent or progressive high-grade gliomas received 120 mg/m\^2/dose of INCB7839 orally, twice a day for 28-day cycles. Treatment could continue for up to 26 courses (approximately 2 years) in the absence of disease progression or unacceptable toxicity or another off treatment or off study reason.
Time to Reach Maximum Concentration [Tmax] of INCB7839	4.0 hours Interval 3.9 to 8.4

SECONDARY outcome

Timeframe: 3 months from first dose of INCB7839

Population: Of 12 eligible subjects enrolled, 1 did not start therapy and therefore was not evaluable for efficacy evaluation and estimation of PFS.

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 outcome measure.

Outcome measures

Outcome measures
Measure	Dose Level 1 (120 mg/m^2/Dose) n=11 Participants Subjects with recurrent or progressive high-grade gliomas received 120 mg/m\^2/dose of INCB7839 orally, twice a day for 28-day cycles. Treatment could continue for up to 26 courses (approximately 2 years) in the absence of disease progression or unacceptable toxicity or another off treatment or off study reason.
Percent Probability of Progression-free Survival	18.18 Percent probability Interval 0.0 to 40.97

SECONDARY outcome

Timeframe: 3 months from first dose of INCB7839

Population: Of 12 eligible subjects enrolled, 1 did not start therapy and therefore was not evaluable for efficacy evaluation and estimation of overall survival.

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.

Outcome measures

Outcome measures
Measure	Dose Level 1 (120 mg/m^2/Dose) n=11 Participants Subjects with recurrent or progressive high-grade gliomas received 120 mg/m\^2/dose of INCB7839 orally, twice a day for 28-day cycles. Treatment could continue for up to 26 courses (approximately 2 years) in the absence of disease progression or unacceptable toxicity or another off treatment or off study reason.
Percent Probability of Overall Survival	53.69 Percent probability Interval 17.02 to 90.36

SECONDARY outcome

Timeframe: Up to 2 years following last dose of INCB7839

Population: Of 12 eligible subjects enrolled, 1 did not start therapy and therefore was not evaluable for response. Among 11 eligible, evaluable subjects, none had complete or partial responses, and it was not possible to calculate duration of response.

Complete or partial responses were considered responses. Response was evaluated by imaging or clinical progression. Duration of response was measured from the time measurement criteria were met for complete or partial response until the first date that recurrent or progressive disease was objectively documented.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Day 14 of Course 1

Population: Eligible subjects with HER2 ECD data were included in this analysis. Ten participants had data at baseline and 9 had data at day 14 of course 1.

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

Outcome measures

Outcome measures
Measure	Dose Level 1 (120 mg/m^2/Dose) n=10 Participants Subjects with recurrent or progressive high-grade gliomas received 120 mg/m\^2/dose of INCB7839 orally, twice a day for 28-day cycles. Treatment could continue for up to 26 courses (approximately 2 years) in the absence of disease progression or unacceptable toxicity or another off treatment or off study reason.
ADAM10 Inhibition of HER2 Baseline	16.66 ng/ml Interval 4.24 to 37.26
ADAM10 Inhibition of HER2 Course 1, Day 14	17.55 ng/ml Interval 4.64 to 114.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 30 days post treatment.

Population: No samples were received for this exploratory objective.

Descriptive statistics for neuroligin-3 (NLGN3) in cerebral spinal fluid will be reported.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 30 days post treatment

Population: No samples were received for this exploratory objective.

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

Outcome measures

Outcome data not reported

Adverse Events

Dose Level 1 (120 mg/m^2/Dose)

Serious events: 9 serious events

Other events: 10 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Dose Level 1 (120 mg/m^2/Dose) n=11 participants at risk Subjects with recurrent or progressive high-grade gliomas received 120 mg/m\^2/dose of INCB7839 orally, twice a day for 28-day cycles. Treatment could continue for up to 26 courses (approximately 2 years) in the absence of disease progression or unacceptable toxicity or another off treatment or off study reason.
Blood and lymphatic system disorders Anemia	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Gastrointestinal disorders Constipation	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Gastrointestinal disorders Vomiting	18.2% 2/11 • Number of events 2 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
General disorders Death NOS	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
General disorders Disease progression	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
General disorders Fatigue	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Infections and infestations Lung infection	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Infections and infestations Sepsis	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Infections and infestations Thrush	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Investigations Alanine aminotransferase increased	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Investigations Lymphocyte count decreased	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Investigations White blood cell decreased	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Metabolism and nutrition disorders Hyperkalemia	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Nervous system disorders Ataxia	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Nervous system disorders Cerebral Venous Thrombosis	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Nervous system disorders Depressed level of consciousness	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Nervous system disorders Dysarthria	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Nervous system disorders Encephalopathy	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Nervous system disorders Headache	18.2% 2/11 • Number of events 2 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Nervous system disorders Hydrocephalus	36.4% 4/11 • Number of events 4 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Nervous system disorders Intracranial hemorrhage	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Nervous system disorders Paroxysmal Sympathetic Hyperactivity	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Nervous system disorders Posterior Reversible Encephalopathy Syndrome	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Nervous system disorders Seizure	18.2% 2/11 • Number of events 3 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Nervous system disorders Somnolence	18.2% 2/11 • Number of events 2 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Nervous system disorders Spasticity	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Respiratory, thoracic and mediastinal disorders Respiratory failure	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Skin and subcutaneous tissue disorders Skin ulceration	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.

Other adverse events

Other adverse events
Measure	Dose Level 1 (120 mg/m^2/Dose) n=11 participants at risk Subjects with recurrent or progressive high-grade gliomas received 120 mg/m\^2/dose of INCB7839 orally, twice a day for 28-day cycles. Treatment could continue for up to 26 courses (approximately 2 years) in the absence of disease progression or unacceptable toxicity or another off treatment or off study reason.
Blood and lymphatic system disorders Anemia	27.3% 3/11 • Number of events 10 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Ear and labyrinth disorders Vertigo	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Eye disorders Dry eye	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Gastrointestinal disorders Constipation	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Gastrointestinal disorders Diarrhea	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Gastrointestinal disorders Nausea	27.3% 3/11 • Number of events 3 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Gastrointestinal disorders Vomiting	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
General disorders Fatigue	45.5% 5/11 • Number of events 6 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
General disorders Fever	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Investigations Alanine aminotransferase increased	72.7% 8/11 • Number of events 13 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Investigations Aspartate aminotransferase increased	36.4% 4/11 • Number of events 6 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Investigations Hemoglobin increased	18.2% 2/11 • Number of events 3 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Investigations Lymphocyte count decreased	54.5% 6/11 • Number of events 26 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Investigations Platelet count decreased	36.4% 4/11 • Number of events 8 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Investigations White blood cell decreased	36.4% 4/11 • Number of events 8 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Metabolism and nutrition disorders Anorexia	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Metabolism and nutrition disorders Hyperkalemia	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Metabolism and nutrition disorders Hypoalbuminemia	45.5% 5/11 • Number of events 10 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Metabolism and nutrition disorders Hypocalcemia	9.1% 1/11 • Number of events 2 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Metabolism and nutrition disorders Hypokalemia	27.3% 3/11 • Number of events 4 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Metabolism and nutrition disorders Hypomagnesemia	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Metabolism and nutrition disorders Hyponatremia	18.2% 2/11 • Number of events 2 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Metabolism and nutrition disorders Hypophosphatemia	27.3% 3/11 • Number of events 7 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Nervous system disorders Headache	18.2% 2/11 • Number of events 2 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Nervous system disorders Somnolence	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Skin and subcutaneous tissue disorders Dry skin	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Investigations Neutrophil count decreased	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.
Blood and lymphatic system disorders Leukocytosis	9.1% 1/11 • Number of events 1 • Adverse events were collected while participants were on protocol therapy and up to 6 months while in follow-up Only eligible subjects that started therapy were included in adverse event (AE) reporting (n=11). As per protocol, grade 1-2 AEs that were at least possibly related to drug and all grade 3-5 AEs regardless of attribution to study drug were recorded. AEs were graded using CTCAE v5.0. Serious AEs included those that were life-threatening or AEs requiring intervention, resulting in death, hospitalization, disability, congenital anomaly/birth defect or otherwise marked serious in Rave.

Additional Information

Catherine Billups

PediatricBTC

Phone: 901-595-3370

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place