Trial Outcomes & Findings for Infigratinib in Recurrent High-Grade Glioma Patients (NCT NCT04424966)

Last Updated: 2025-10-24

Results Overview

Phase 0: Total infigratinib concentration in Gd enhancing and Gd non-enhancing tumor tissue collected intraoperatively, approximately 8 hours after study drug administration, will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.

Recruitment status

TERMINATED

Study phase

EARLY_PHASE1

Target enrollment

7 participants

Primary outcome timeframe

Intraoperative

Results posted on

2025-10-24

Participant Flow

Participant milestones

Participant milestones
Measure	Recurrent High Grade Glioma Participants with recurrent high grade glioma with FGFR1 K656E mutation, or FGFR3 K650E mutation, or FGFR3-TACC3 translocation who are scheduled for surgical resection. 125 mg of infigratinib will be administered orally for 7 days prior to surgical resection during the Phase 0 component. Participants with tumors demonstrating positive PK response will continue treatment in the expansion phase component. 125 mg of infigratinib will be administered orally for 21 consecutive days during 28-day treatment cycles during the expansion phase component.
Phase 0 STARTED	7
Phase 0 COMPLETED	7
Phase 0 NOT COMPLETED	0
Expansion Phase STARTED	3
Expansion Phase COMPLETED	3
Expansion Phase NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Infigratinib in Recurrent High-Grade Glioma Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Recurrent High Grade Glioma n=7 Participants Participants with recurrent high grade glioma with FGFR1 K656E mutation, or FGFR3 K650E mutation, or FGFR3-TACC3 translocation who are scheduled for surgical resection. 125 mg of infigratinib will be administered orally for 7 days prior to surgical resection during the Phase 0 component. Participants with tumors demonstrating positive PK response will continue treatment in the expansion phase component. 125 mg of infigratinib will be administered orally for 21 consecutive days during 28-day treatment cycles during the expansion phase component.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants
Age, Continuous	63 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: Intraoperative

Outcome measures

Outcome measures
Measure	Recurrent High Grade Glioma n=7 Participants Participants with recurrent high grade glioma with FGFR1 K656E mutation, or FGFR3 K650E mutation, or FGFR3-TACC3 translocation who are scheduled for surgical resection. 125 mg of infigratinib will be administered orally for 7 days prior to surgical resection during the Phase 0 component. Participants with tumors demonstrating positive PK response will continue treatment in the expansion phase component. 125 mg of infigratinib will be administered orally for 21 consecutive days during 28-day treatment cycles during the expansion phase component.
Total Concentration of Infigratinib in Enhancing and Non-Enhancing Tumor Tissue Total Concentration of Infigratinib in Enhancing Tissue	790.6 nM Interval 425.0 to 1259.1
Total Concentration of Infigratinib in Enhancing and Non-Enhancing Tumor Tissue Total Concentration of Infigratinib in Non-enhancing Tissue	628.4 nM Interval 86.4 to 1524.5

PRIMARY outcome

Timeframe: Intraoperative

Phase 0: Unbound infigratinib concentration in Gd enhancing and Gd non-enhancing tumor tissue collected intraoperatively, approximately 8 hours after study drug administration, will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.

Outcome measures

Outcome measures
Measure	Recurrent High Grade Glioma n=7 Participants Participants with recurrent high grade glioma with FGFR1 K656E mutation, or FGFR3 K650E mutation, or FGFR3-TACC3 translocation who are scheduled for surgical resection. 125 mg of infigratinib will be administered orally for 7 days prior to surgical resection during the Phase 0 component. Participants with tumors demonstrating positive PK response will continue treatment in the expansion phase component. 125 mg of infigratinib will be administered orally for 21 consecutive days during 28-day treatment cycles during the expansion phase component.
Unbound Concentration of Infigratinib in Enhancing and Non-Enhancing Tumor Tissue Unbound Concentration of Infigratinib in Enhancing Tissue	4.4 nM Interval 1.2 to 9.1
Unbound Concentration of Infigratinib in Enhancing and Non-Enhancing Tumor Tissue Unbound Concentration of Infigratinib in Non-enhancing Tissue	3.5 nM Interval 0.7 to 11.3

PRIMARY outcome

Timeframe: Intraoperative

Phase 0: Total infigratinib concentration in blood plasma collected intraoperatively, approximately 8 hours after study drug administration, will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.

Outcome measures

Outcome measures
Measure	Recurrent High Grade Glioma n=7 Participants Participants with recurrent high grade glioma with FGFR1 K656E mutation, or FGFR3 K650E mutation, or FGFR3-TACC3 translocation who are scheduled for surgical resection. 125 mg of infigratinib will be administered orally for 7 days prior to surgical resection during the Phase 0 component. Participants with tumors demonstrating positive PK response will continue treatment in the expansion phase component. 125 mg of infigratinib will be administered orally for 21 consecutive days during 28-day treatment cycles during the expansion phase component.
Total Concentration of Infigratinib in Plasma Unbound Concentration of Infigratinib in Plasma	0.8 nM Interval 0.4 to 2.6
Total Concentration of Infigratinib in Plasma Total Concentration of Infigratinib in Plasma	146.1 nM Interval 56.4 to 334.3

PRIMARY outcome

Timeframe: Intraoperative

Phase 0: Unbound infigratinib concentration in blood plasma collected intraoperatively, approximately 8 hours after study drug administration, will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.

Outcome measures

Outcome measures
Measure	Recurrent High Grade Glioma n=7 Participants Participants with recurrent high grade glioma with FGFR1 K656E mutation, or FGFR3 K650E mutation, or FGFR3-TACC3 translocation who are scheduled for surgical resection. 125 mg of infigratinib will be administered orally for 7 days prior to surgical resection during the Phase 0 component. Participants with tumors demonstrating positive PK response will continue treatment in the expansion phase component. 125 mg of infigratinib will be administered orally for 21 consecutive days during 28-day treatment cycles during the expansion phase component.
Unbound Concentration of Infigratinib in Plasma	0.8 nM Interval 0.4 to 2.6

PRIMARY outcome

Timeframe: Intraoperative

Phase 0: Total infigratinib concentration in cerebrospinal fluid (CSF) collected intraoperatively, approximately 8 hours after study drug administration, will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.

Outcome measures

Outcome measures
Measure	Recurrent High Grade Glioma n=7 Participants Participants with recurrent high grade glioma with FGFR1 K656E mutation, or FGFR3 K650E mutation, or FGFR3-TACC3 translocation who are scheduled for surgical resection. 125 mg of infigratinib will be administered orally for 7 days prior to surgical resection during the Phase 0 component. Participants with tumors demonstrating positive PK response will continue treatment in the expansion phase component. 125 mg of infigratinib will be administered orally for 21 consecutive days during 28-day treatment cycles during the expansion phase component.
Total Concentration of Infigratinib in Cerebrospinal Fluid (CSF) Total Concentration of Infigratinib in CSF	7.1 nM Interval 1.6 to 38.3
Total Concentration of Infigratinib in Cerebrospinal Fluid (CSF) Unbound Concentration of Infigratinib in CSF	7.1 nM Interval 1.6 to 38.3

PRIMARY outcome

Timeframe: Intraoperative

Phase 0: Unbound infigratinib concentration in cerebrospinal fluid (CSF) collected intraoperatively, approximately 8 hours after study drug administration, will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.

Outcome measures

Outcome measures
Measure	Recurrent High Grade Glioma n=7 Participants Participants with recurrent high grade glioma with FGFR1 K656E mutation, or FGFR3 K650E mutation, or FGFR3-TACC3 translocation who are scheduled for surgical resection. 125 mg of infigratinib will be administered orally for 7 days prior to surgical resection during the Phase 0 component. Participants with tumors demonstrating positive PK response will continue treatment in the expansion phase component. 125 mg of infigratinib will be administered orally for 21 consecutive days during 28-day treatment cycles during the expansion phase component.
Unbound Concentration of Infigratinib in Cerebrospinal Fluid (CSF)	7.1 nM Interval 1.6 to 38.3

PRIMARY outcome

Timeframe: From the date of Phase 0 surgery until the first documentation of disease progression or death due to any cause, assessed up to 6 months

Population: Participants who enrolled into the expansion phase component of the study. Participants alive without progression at 6 months were censored for PFS at the date of their last tumor assessment.

Proportion of participants who remain alive without disease progression at 6 months

Outcome measures

Outcome measures
Measure	Recurrent High Grade Glioma n=3 Participants Participants with recurrent high grade glioma with FGFR1 K656E mutation, or FGFR3 K650E mutation, or FGFR3-TACC3 translocation who are scheduled for surgical resection. 125 mg of infigratinib will be administered orally for 7 days prior to surgical resection during the Phase 0 component. Participants with tumors demonstrating positive PK response will continue treatment in the expansion phase component. 125 mg of infigratinib will be administered orally for 21 consecutive days during 28-day treatment cycles during the expansion phase component.
6-month Progression-Free Survival (PFS6) in Expansion Phase Participants	66.7 Percent

SECONDARY outcome

Timeframe: Baseline, Intraoperatively

Population: 1 participant was not assessed due to insufficient tissue for analysis.

Phase 0: The mean percentage change of pERK positive cells in resected post-treatment recurrent high-grade glioma tumor tissue compared to baseline (archival primary high-grade glioma tumor tissue collected at screening) will be quantified using immunohistochemistry.

Outcome measures

Outcome measures
Measure	Recurrent High Grade Glioma n=6 Participants Participants with recurrent high grade glioma with FGFR1 K656E mutation, or FGFR3 K650E mutation, or FGFR3-TACC3 translocation who are scheduled for surgical resection. 125 mg of infigratinib will be administered orally for 7 days prior to surgical resection during the Phase 0 component. Participants with tumors demonstrating positive PK response will continue treatment in the expansion phase component. 125 mg of infigratinib will be administered orally for 21 consecutive days during 28-day treatment cycles during the expansion phase component.
Mean % Change of pERK+ Cells in Resected Post-Treatment Recurrent HGG Tissue vs Baseline Tissue	17.31 Percentage of cells Interval -27.08 to 92.61

SECONDARY outcome

Timeframe: Baseline, Intraoperatively

Population: 1 participant was not assessed due to insufficient tissue for analysis.

Phase 0: The mean percentage change of MIB-1 positive cells in resected post-treatment recurrent high-grade glioma tumor tissue compared to baseline (archival primary high-grade glioma tumor tissue collected at screening) will be quantified using immunohistochemistry.

Outcome measures

Outcome measures
Measure	Recurrent High Grade Glioma n=6 Participants Participants with recurrent high grade glioma with FGFR1 K656E mutation, or FGFR3 K650E mutation, or FGFR3-TACC3 translocation who are scheduled for surgical resection. 125 mg of infigratinib will be administered orally for 7 days prior to surgical resection during the Phase 0 component. Participants with tumors demonstrating positive PK response will continue treatment in the expansion phase component. 125 mg of infigratinib will be administered orally for 21 consecutive days during 28-day treatment cycles during the expansion phase component.
Mean % Change of MIB-1+ Cells in Resected Post-Treatment Recurrent HGG Tissue vs Baseline Tissue	-7.39 Percentage of cells Interval -17.28 to 2.88

SECONDARY outcome

Timeframe: Baseline, Intraoperatively

Population: 1 participant was not assessed due to insufficient tissue for analysis.

Phase 0: The mean percentage change of ClCase3 positive cells in resected post-treatment recurrent high-grade glioma tumor tissue compared to baseline (archival primary high-grade glioma tumor tissue collected at screening) will be quantified using immunohistochemistry.

Outcome measures

Outcome measures
Measure	Recurrent High Grade Glioma n=6 Participants Participants with recurrent high grade glioma with FGFR1 K656E mutation, or FGFR3 K650E mutation, or FGFR3-TACC3 translocation who are scheduled for surgical resection. 125 mg of infigratinib will be administered orally for 7 days prior to surgical resection during the Phase 0 component. Participants with tumors demonstrating positive PK response will continue treatment in the expansion phase component. 125 mg of infigratinib will be administered orally for 21 consecutive days during 28-day treatment cycles during the expansion phase component.
Mean % Change of ClCas3+ Cells in Resected Post-Treatment Recurrent HGG Tissue vs Baseline Tissue	0.19 Percentage of cells Interval -27.71 to 35.48

SECONDARY outcome

Timeframe: From date of first dose until 7 days after last dose, assessed over 2 years 6 months

Population: The analysis population includes participants who took at least one dose of the study drug.

Expansion Phase: An AE that began after the start of study medication treatment; or if the event was continuous from baseline and was serious, study medication-related, or resulted in death, discontinuation, or interruption or reduction of trial therapy.

Outcome measures

Outcome measures
Measure	Recurrent High Grade Glioma n=7 Participants Participants with recurrent high grade glioma with FGFR1 K656E mutation, or FGFR3 K650E mutation, or FGFR3-TACC3 translocation who are scheduled for surgical resection. 125 mg of infigratinib will be administered orally for 7 days prior to surgical resection during the Phase 0 component. Participants with tumors demonstrating positive PK response will continue treatment in the expansion phase component. 125 mg of infigratinib will be administered orally for 21 consecutive days during 28-day treatment cycles during the expansion phase component.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Assessed by CTCAE v5.0	5 Participants

SECONDARY outcome

Timeframe: From date of first dose until 7 days after last dose, assessed over 2 years 6 months

Population: The analysis population includes participants who took at least one dose of the study drug.

Expansion Phase: TRAEs are those deemed definitely, probably, and potentially related to the study drug.

Outcome measures

Outcome measures
Measure	Recurrent High Grade Glioma n=7 Participants Participants with recurrent high grade glioma with FGFR1 K656E mutation, or FGFR3 K650E mutation, or FGFR3-TACC3 translocation who are scheduled for surgical resection. 125 mg of infigratinib will be administered orally for 7 days prior to surgical resection during the Phase 0 component. Participants with tumors demonstrating positive PK response will continue treatment in the expansion phase component. 125 mg of infigratinib will be administered orally for 21 consecutive days during 28-day treatment cycles during the expansion phase component.
Number of Participants With Treatment-Related Adverse Events (TRAEs) Assessed by CTCAE v5.0	5 Participants

SECONDARY outcome

Timeframe: From date of first dose until 30 days after last dose, assessed over 2 years 6 months

Population: The analysis population includes participants who took at least one dose of the study drug.

Expansion Phase: AE severity as defined according to CTCAE v5.0.

Outcome measures

Outcome measures
Measure	Recurrent High Grade Glioma n=7 Participants Participants with recurrent high grade glioma with FGFR1 K656E mutation, or FGFR3 K650E mutation, or FGFR3-TACC3 translocation who are scheduled for surgical resection. 125 mg of infigratinib will be administered orally for 7 days prior to surgical resection during the Phase 0 component. Participants with tumors demonstrating positive PK response will continue treatment in the expansion phase component. 125 mg of infigratinib will be administered orally for 21 consecutive days during 28-day treatment cycles during the expansion phase component.
Number of Participants With Serious Adverse Events	0 Participants

Adverse Events

Recurrent High Grade Glioma

Serious events: 0 serious events

Other events: 5 other events

Deaths: 6 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Recurrent High Grade Glioma n=7 participants at risk Participants with recurrent high grade glioma with FGFR1 K656E mutation, or FGFR3 K650E mutation, or FGFR3-TACC3 translocation who are scheduled for surgical resection. 125 mg of infigratinib will be administered orally for 7 days prior to surgical resection during the Phase 0 component. Participants with tumors demonstrating positive PK response will continue treatment in the expansion phase component. 125 mg of infigratinib will be administered orally for 21 consecutive days during 28-day treatment cycles during the expansion phase component.
Gastrointestinal disorders Diarrhea	28.6% 2/7 • Number of events 4 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Gastrointestinal disorders Nausea	42.9% 3/7 • Number of events 3 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Gastrointestinal disorders Constipation	28.6% 2/7 • Number of events 2 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Gastrointestinal disorders Gastrooesophageal reflux disease	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Gastrointestinal disorders Dyspepsia	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Gastrointestinal disorders Aphthous ulcer	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Gastrointestinal disorders Abdominal pain	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Gastrointestinal disorders Dry mouth	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Metabolism and nutrition disorders Hyperphosphataemia	14.3% 1/7 • Number of events 3 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Metabolism and nutrition disorders Decreased appetite	14.3% 1/7 • Number of events 2 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Metabolism and nutrition disorders Hypokalaemia	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Nervous system disorders Headache	28.6% 2/7 • Number of events 2 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Nervous system disorders Ageusia	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Nervous system disorders Tremor	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Nervous system disorders Disturbance in attention	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Nervous system disorders Dizziness	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Psychiatric disorders Depression	28.6% 2/7 • Number of events 2 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Psychiatric disorders Insomnia	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Psychiatric disorders Agitation	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
General disorders Fatigue	42.9% 3/7 • Number of events 3 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
General disorders Asthenia	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Eye disorders Vision blurred	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Eye disorders Dry eye	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Skin and subcutaneous tissue disorders Dry skin	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Infections and infestations Urinary tract infection	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Infections and infestations Bacteriuria	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Ear and labyrinth disorders Deafness	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Musculoskeletal and connective tissue disorders Tendon disorder	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Vascular disorders Deep vein thrombosis	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Injury, poisoning and procedural complications Fall	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months
Investigations Weight decreased	14.3% 1/7 • Number of events 1 • From the day of first enrollment until 7 days after the final participant's final visit, approximately 2 years 6 months

Additional Information

Dr. Nader Sanai

Ivy Brain Tumor Center

Phone: 602-406-8605

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place