Infigratinib in Recurrent High-Grade Glioma Patients

A Phase 0 Study of Infigratinib in Recurrent High-Grade Glioma Participants Scheduled for Resection to Evaluate Central Nervous System (CNS) Penetration With PK Triggered Expansion Cohort

Status

Terminated

Phases

Early Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04424966

Enrollment

Registered

2020-06-11

Start date

2020-07-21

Completion date

2024-02-19

Last updated

2025-10-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Glioma, Glioblastoma, GBM

Brief summary

This trial is an open-label, multicenter, Phase 0 trial that will enroll up to 20 participants with recurrent high-grade glioma with FGFR1 K656E or FGFR3 K650E mutation or FGFR3-TACC3 translocation which are scheduled for resection. In the lead-in cohort, a total of 20 participants will be enrolled into the proposed phase 0 clinical trial. Participants will be administered infigratinib prior to surgical resection of their tumor.

Interventions

DRUGInfigratinib

The Phase 0 study will include treatment of recurrent high-grade glioma participants with 125 mg of infigratinib 7 days prior to surgical resection. Participants with tumors demonstrating PK-response will continue treatment with the same dose continuously for 21 days in 28-day cycles after surgery.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Prior resection of histologically diagnosed high-grade gliomas (III and IV) defined as participants who have progressed on or following standard (Stupp regimen) therapy, which included maximal surgical resection, temozolomide, and fractionated radiotherapy. 2. Recurrence must be confirmed by diagnostic biopsy with local pathology review or contrast-enhanced MRI. 3. Have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 2 perpendicular measurements of at least 1 cm, as per RANO criteria. 4. Sufficient archival tissue available to confirm eligibility. 5. Archival tissue must demonstrate: FGFR1 K656E or FGFR3 K650E mutation or FGFR3-TACC3 translocation from NGS sequencing or IHC and RT-PCR. 6. Ability to understand and the willingness to sign a written informed consent document (personally or by the legally authorized representative, if applicable). 7. Has voluntarily agreed to participate by giving written informed consent (personally or via legally authorized representative(s), and assent if applicable). Written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness. 8. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures. 9. Age ≥18 at time of consent 10. Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology (Group (ECOG) scale (Oken et al. 1982) 11. Ability to swallow oral medications. 12. Has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility): 1. Adequate bone marrow function: * absolute neutrophil count ≥1,000/mcL * Platelets (at time of surgery) ≥100,000/mcL * hemoglobin ≥8.0 g/dL Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. 2. Adequate hepatic and renal function: * total bilirubin ≤1.5 X ULN Participants with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted. * AST(SGOT) ≤3 X institutional ULN * ALT(SGPT) ≤3 X institutional ULN * Calculated or measured creatinine clearance ≥45 mL/min 3. Other Lab Values: * Amylase or lipase ≤2 X institutional ULN * calcium or phosphorus, or calcium-phosphorus product \<55 mg2/dL2  1. Inorganic phosphorus within normal limits 2. Total corrected serum calcium within normal limits 13. Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or participant has had a hysterectomy. 14. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 3 months after the end of treatment administration. 15. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner and for an additional 1 month after the end of treatment administration. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner to prevent delivery of the drug via seminal fluid. 16. Agreement to adhere to Lifestyle Considerations throughout study duration. 17. Participants who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to Day 1. A washout period of at least 21 days is required between last chemotherapy dose and Day 1 (provided the patient did not receive radiotherapy). 18. Participants who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and Day 1.

Exclusion criteria

1. Have a history of liver transplant. 2. Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection). 3. Known active systemic bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Screening is not required for enrollment. 4. Have a history and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, vascular system, and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification. 5. Have current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy, inflammation or ulceration, keratoconjunctivitis confirmed by ophthalmic examination. Subjects with asymptomatic ophthalmic conditions assessed by the investigator to pose minimal risk for study participation may be enrolled in the study. 6. Have current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc. 7. Have had a recent (≤3 months prior to first dose of study drug) transient ischemic attack or stroke. 8. CTCAE (v5.0) Grade ≥2 hearing loss. 9. CTCAE (v5.0) Grade ≥2 neuropathy. 10. Have clinically significant cardiac disease including any of the following: 1. Known congestive heart failure requiring treatment (New York Heart Association Grade ≥2), LVEF \<50% or local lower limit of normal as determined by MUGA scan or echocardiogram (ECHO), or uncontrolled hypertension (refer to the European Society of Cardiology and European Society of Hypertension guidelines \[Williams et al 2018\]). 2. Presence of Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade ≥2 ventricular arrhythmias, atrial fibrillation, bradycardia, or conduction abnormality. 3. Unstable angina pectoris or acute myocardial infarction ≤3 months prior to first dose of study drug. 4. QTcF \>470 msec (males and females). Note: If the QTcF is \>470 msec in the first ECG, a total of 3 ECGs separated by at least 5 minutes should be performed. If the average of these 3 consecutive results for QTcF is ≤470 msec, the participant meets eligibility in this regard. 5. Known history of congenital long QT syndrome. 11. Has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea). 12. Prior therapy with any mitogen-activated protein kinase (MEK) or FGFR inhibitor. Prior therapy is defined as a therapeutic dosing, as determined by the Investigator. 13. Are currently receiving or are planning to receive during participation in this study, treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration. Participants are not permitted to receive enzyme-inducing anti-epileptic drugs, including carbamazepine, phenytoin, phenobarbital, and primidone. 14. Current use of coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed. 15. Have any known hypersensitivity to gemcitabine, cisplatin, calcium-lowering agents, infigratinib, or their excipients. 16. Treatment with another investigational drug or other intervention within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer. 17. Have consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges or products containing juice of these fruits within 7 days prior to first dose of study drug. 18. Have used medications known to prolong the QT interval and/or are associated with a risk of Torsades de Pointes (TdP) 7 days prior to first dose of study drug. 19. Have used amiodarone within 90 days prior to first dose of study drug.

Design outcomes

Primary

Measure	Time frame	Description
Total Concentration of Infigratinib in Enhancing and Non-Enhancing Tumor Tissue	Intraoperative	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.
6-month Progression-Free Survival (PFS6) in Expansion Phase Participants	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	Proportion of participants who remain alive without disease progression at 6 months
Unbound Concentration of Infigratinib in Cerebrospinal Fluid (CSF)	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.
Total Concentration of Infigratinib in Cerebrospinal Fluid (CSF)	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.
Unbound Concentration of Infigratinib in Plasma	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.
Total Concentration of Infigratinib in Plasma	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.
Unbound Concentration of Infigratinib in Enhancing and Non-Enhancing Tumor Tissue	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.

Secondary

Measure	Time frame	Description
Mean % Change of ClCas3+ Cells in Resected Post-Treatment Recurrent HGG Tissue vs Baseline Tissue	Baseline, Intraoperatively	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.
Mean % Change of pERK+ Cells in Resected Post-Treatment Recurrent HGG Tissue vs Baseline Tissue	Baseline, Intraoperatively	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.
Mean % Change of MIB-1+ Cells in Resected Post-Treatment Recurrent HGG Tissue vs Baseline Tissue	Baseline, Intraoperatively	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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Assessed by CTCAE v5.0	From date of first dose until 7 days after last dose, assessed over 2 years 6 months	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.
Number of Participants With Treatment-Related Adverse Events (TRAEs) Assessed by CTCAE v5.0	From date of first dose until 7 days after last dose, assessed over 2 years 6 months	Expansion Phase: TRAEs are those deemed definitely, probably, and potentially related to the study drug.
Number of Participants With Serious Adverse Events	From date of first dose until 30 days after last dose, assessed over 2 years 6 months	Expansion Phase: AE severity as defined according to CTCAE v5.0.

Other

Measure	Time frame	Description
Total Infigratinib Time to Peak Plasma Concentration (Tmax)	Day of surgery at pre-dose and 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose	Phase 0: Total infigratinib time to peak plasma concentration (Tmax) in blood plasma will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.
Unbound Infigratinib Peak Plasma Concentration (Cmax)	Day of surgery at pre-dose and 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose	Phase 0: Unbound infigratinib peak plasma concentration (Cmax) in blood plasma will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.
Unbound Infigratinib Area Under the Plasma Concentration Versus Time Curve (AUC)	Day of surgery at pre-dose and 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose	Phase 0: Unbound infigratinib area under the plasma concentration versus time curve (AUC) in blood plasma will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.
Total Infigratinib Area Under the Plasma Concentration Versus Time Curve (AUC)	Day of surgery at pre-dose and 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose	Phase 0: Total infigratinib area under the plasma concentration versus time curve (AUC) in blood plasma will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.
Median Overall Survival (OS)	From the date of Phase 0 surgery until the date of death due to any cause, assessed over 2 years 6 months	Expansion Phase: The number of days from the date of Phase 0 surgery until the date of death due to any cause.
Unbound Infigratinib Concentration Half-Life (T1/2)	Day of surgery at pre-dose and 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose	Phase 0: Unbound infigratinib concentration half-life (T1/2) in blood plasma will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.
Total Infigratinib Concentration Half-Life (T1/2)	Day of surgery at pre-dose and 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose	Phase 0: Total infigratinib concentration half-life (T1/2) in blood plasma will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.
Total Infigratinib Peak Plasma Concentration (Cmax)	Day of surgery at pre-dose and 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose	Phase 0: Total infigratinib peak plasma concentration (Cmax) in blood plasma will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.
Unbound Infigratinib Time to Peak Plasma Concentration (Tmax)	Day of surgery at pre-dose and 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose	Phase 0: Unbound infigratinib time to peak plasma concentration (Tmax) in blood plasma will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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.	7
Total	7

Arm

Count

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.

Total

Baseline characteristics

Characteristic	Recurrent High Grade Glioma
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	3 Participants
Age, Categorical Between 18 and 65 years	4 Participants
Age, Continuous	63 years
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	7 Participants
Region of Enrollment United States	7 Participants
Sex: Female, Male Female	3 Participants
Sex: Female, Male Male	4 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	6 / 7
other Total, other adverse events	5 / 7
serious Total, serious adverse events	0 / 7

Outcome results

Primary

6-month Progression-Free Survival (PFS6) in Expansion Phase Participants

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

Time frame: 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.

Arm	Measure	Value (NUMBER)
Arm 1	6-month Progression-Free Survival (PFS6) in Expansion Phase Participants	66.7 Percent

Primary

Total Concentration of Infigratinib in Cerebrospinal Fluid (CSF)

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.

Time frame: Intraoperative

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Arm 1	Total Concentration of Infigratinib in Cerebrospinal Fluid (CSF)	Total Concentration of Infigratinib in CSF	7.1 nM
Arm 1	Total Concentration of Infigratinib in Cerebrospinal Fluid (CSF)	Unbound Concentration of Infigratinib in CSF	7.1 nM

Primary

Total Concentration of Infigratinib in Enhancing and Non-Enhancing Tumor Tissue

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.

Time frame: Intraoperative

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Arm 1	Total Concentration of Infigratinib in Enhancing and Non-Enhancing Tumor Tissue	Total Concentration of Infigratinib in Enhancing Tissue	790.6 nM
Arm 1	Total Concentration of Infigratinib in Enhancing and Non-Enhancing Tumor Tissue	Total Concentration of Infigratinib in Non-enhancing Tissue	628.4 nM

Primary

Total Concentration of Infigratinib in Plasma

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.

Time frame: Intraoperative

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Arm 1	Total Concentration of Infigratinib in Plasma	Total Concentration of Infigratinib in Plasma	146.1 nM
Arm 1	Total Concentration of Infigratinib in Plasma	Unbound Concentration of Infigratinib in Plasma	0.8 nM

Primary

Unbound Concentration of Infigratinib in Cerebrospinal Fluid (CSF)

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.

Time frame: Intraoperative

Arm	Measure	Value (GEOMETRIC_MEAN)
Arm 1	Unbound Concentration of Infigratinib in Cerebrospinal Fluid (CSF)	7.1 nM

Primary

Unbound Concentration of Infigratinib in Enhancing and Non-Enhancing Tumor Tissue

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.

Time frame: Intraoperative

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Arm 1	Unbound Concentration of Infigratinib in Enhancing and Non-Enhancing Tumor Tissue	Unbound Concentration of Infigratinib in Enhancing Tissue	4.4 nM
Arm 1	Unbound Concentration of Infigratinib in Enhancing and Non-Enhancing Tumor Tissue	Unbound Concentration of Infigratinib in Non-enhancing Tissue	3.5 nM

Primary

Unbound Concentration of Infigratinib in Plasma

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.

Time frame: Intraoperative

Arm	Measure	Value (GEOMETRIC_MEAN)
Arm 1	Unbound Concentration of Infigratinib in Plasma	0.8 nM

Secondary

Mean % Change of ClCas3+ Cells in Resected Post-Treatment Recurrent HGG Tissue vs Baseline Tissue

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.

Time frame: Baseline, Intraoperatively

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

Arm	Measure	Value (MEAN)
Arm 1	Mean % Change of ClCas3+ Cells in Resected Post-Treatment Recurrent HGG Tissue vs Baseline Tissue	0.19 Percentage of cells

Secondary

Mean % Change of MIB-1+ Cells in Resected Post-Treatment Recurrent HGG Tissue vs Baseline Tissue

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.

Time frame: Baseline, Intraoperatively

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

Arm	Measure	Value (MEAN)
Arm 1	Mean % Change of MIB-1+ Cells in Resected Post-Treatment Recurrent HGG Tissue vs Baseline Tissue	-7.39 Percentage of cells

Secondary

Mean % Change of pERK+ Cells in Resected Post-Treatment Recurrent HGG Tissue vs Baseline Tissue

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.

Time frame: Baseline, Intraoperatively

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

Arm	Measure	Value (MEAN)
Arm 1	Mean % Change of pERK+ Cells in Resected Post-Treatment Recurrent HGG Tissue vs Baseline Tissue	17.31 Percentage of cells

Secondary

Number of Participants With Serious Adverse Events

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

Time frame: 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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Arm 1	Number of Participants With Serious Adverse Events	0 Participants

Secondary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Assessed by CTCAE v5.0

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.

Time frame: 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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Arm 1	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Assessed by CTCAE v5.0	5 Participants

Secondary

Number of Participants With Treatment-Related Adverse Events (TRAEs) Assessed by CTCAE v5.0

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

Time frame: 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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Arm 1	Number of Participants With Treatment-Related Adverse Events (TRAEs) Assessed by CTCAE v5.0	5 Participants

Other Pre-specified

Median Overall Survival (OS)

Expansion Phase: The number of days from the date of Phase 0 surgery until the date of death due to any cause.

Time frame: From the date of Phase 0 surgery until the date of death due to any cause, assessed over 2 years 6 months

Other Pre-specified

Total Infigratinib Area Under the Plasma Concentration Versus Time Curve (AUC)

Phase 0: Total infigratinib area under the plasma concentration versus time curve (AUC) in blood plasma will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.