Study With Infigratinib in Subjects With Advanced Solid and CNS Tumors or Recurrent or Progressive Low-Grade Glioma With Selected FGFR1-3 Alterations

NCT05222165 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: INFI-21-072021-005614-34
• Study Type: interventional
• Target: N/A
• Locations: 3 countries
• Sites: 10

Brief Summary

The phase 1b study is aimed at determining the pediatric recommended phase 2 dose (RP2D) of Infigratinib. The phase 2 study will evaluate efficacy and safety of infigratinib.

Conditions

Advanced Solid Tumor; CNS Tumor; Recurrent WHO Grade II Glioma

Keywords

Low-Grade Glioma; FGFR1-3 Mutation or fusion/rearrangements; FGFR1-3 Fusion; FGFR1-3 Rearrangements; Advanced Solid Tumor; CNS Tumor

Outcome Measures

Primary Outcomes (2)

• Phase 1b Dose Limiting Toxicity (DLT) rate

  An adverse event (AE) or abnormal laboratory value that are not clearly due to the underlying disease or extraneous causes, including those AEs and abnormal laboratory values that result in a failure to meet the criteria for re-treatment.

  28 days

• Phase 2 Objective Response Rate (ORR) by Blinded Independent Central Review (BICR)

  The proportion of subjects who achieve a confirmed complete response (CR), confirmed partial response (PR), or confirmed minor response (MR) for subjects with LGG. For other subjects, ORR is defined as proportion of subjects who achieve a confirmed CR or confirmed PR.

  Up to 24 months

Secondary Outcomes (37)

• Phase 1b Pharmacokinetics (PK): Cmax

  Up to 24 months

• Phase 1b Pharmacokinetics (PK): AUC

  Up to 24 months

• Phase 1b Pharmacokinetics (PK): T1/2

  Up to 24 months

• Phase 1b Pharmacokinetics (PK): Tmax

  Up to 24 months

• Phase 1b Pharmacokinetics (PK): CL/F

  Up to 24 months

Study Arms (1)

Infigratinib (BGJ398)

EXPERIMENTAL

Generic name: infigratinib. Dosage forms: 18mg and 25mg sprinkle capsules and 25mg, 75mg, 100mg capsules. Phase 1b Three dose levels escalation until RP2D is determined. Phase 2 * Pediatric patients: dose defined in the phase 1b (RP2D); * Adults: 125 mg. Frequency: once daily for 21 days in each 28-day treatment cycle. Duration: Treatment duration will last up to 26 cycles unless progression, death or unacceptable toxicity occur.

Drug: Infigratinib

Interventions

Infigratinib DRUG

Hard gelatin capsules for oral use

Also known as: BGJ398

Infigratinib (BGJ398)

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase 1b:
• Subject must be ≥ 3 to \<18 years of age at the Screening visit.
• Confirmed diagnosis of one of the following:
• LGG (WHO Grade I or II glioma) based on histology, molecular, and clinical criteria concordant with the WHO Grading of Tumors of the Central Nervous System, including glial or mixed neuronal-glial tumor
• Histologically/cytologically confirmed CNS tumor (other than LGG).
• Histologically/cytologically confirmed advanced solid tumor.
• Disease is recurrent or progressive after standard therapy (at least 1 prior standard therapy appropriate for tumor type and stage of disease unless available standard therapies are considered inadequate for the subject).
• Phase 2 at screening:
• Diagnosis of recurrent or progressive (at least 1 prior standard therapy) LGG (WHO Grade I or II glioma), including glial or mixed neuronal-glial tumor, based on histology, molecular, and clinical criteria concordant with the WHO Grading of Tumors of the Central Nervous System.
• Age 3 years and older at screening visit.
• Phase 1b/2 (all subjects) at screening:
• Able to swallow and retain oral medication.
• Willing to stop consumption of grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges, or products containing juice of these fruits; and have not consumed these within 7 days before the first dose of study drug.
• Willing and able to comply with scheduled visits, treatment plan, and laboratory tests.
• Sex and Contraceptive/Barrier Requirements

You may not qualify if:

• Prior treatment with a FGFR1-3 selective inhibitor.
• Known serious active infection or any clinically significant systemic illness, which in the Investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the subject's ability to tolerate the study drug.
• Received anti-convulsant drugs that are strong inducers of CYP3A4 (i.e., carbamazepine, phenobarbital, phenytoin) within 4 weeks before starting study treatment.
• Currently receiving treatment with agents that are known strong and moderate inducers of CYP3A4 within 4 weeks from start of treatment or inhibitors of CYP3A4 within 1 week from start of treatment, including herbal preparations; medications which increase serum phosphorus and/or calcium concentration; use of a proton-pump inhibitors (e.g., omeprazole) within 4 days prior to start of study therapy or H2 receptor antagonists (e.g., famotidine) within 2 days prior to the start of study therapy.
• Uncontrollable seizures.
• Have current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy; corneal abrasion, inflammation, or ulceration; or 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.
• Have current evidence of endocrine alterations of calcium/phosphate homeostasis (e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis), unless well controlled.
• Have a history and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, vasculature, myocardium, and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, small renal cyst or stone calcifications, and asymptomatic coronary calcification.
• Have impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (e.g., active ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
• Had major surgery within 2 weeks of enrollment or not fully healed from open wound.

Sponsors & Collaborators

• Helsinn Healthcare SA: lead
• Labcorp Corporation of America Holdings, Inc: collaborator

Study Sites (10)

Lucile Packard Children's Hospital at Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

Children's National Hospital - Brain Tumor Institute

Washington D.C., District of Columbia, 20010-2916, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke Cancer Institute (DCI) - The Preston Robert Tisch Brain Tumor Center

Durham, North Carolina, 27702-3624, United States

Location

UPCM - Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224-1529, United States

Location

University of Alberta - Stollery Children's Hospital (SCH)

Edmonton, Alberta, T6G 2B7, Canada

Location

McMaster Children's Hospital (MCH)

Hamilton, Ontario, L8N 3Z5, Canada

Location

University of Toronto - The Hospital for Sick Children (SickKids)

Toronto, Ontario, M5G 1X8, Canada

Location

Universitaetsklinikum Heidelberg (UKHD) - Zentrum fuer Kinder- und Jugendmedizin - Klinik Kinderheilkunde III

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms

Interventions

infigratinib

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1b: Rolling 6 design, 3 cohorts Phase 2: Single Group Assignment

Study Record Dates

• First Submitted: January 12, 2022
• First Posted: February 3, 2022
• Study Start: October 1, 2021
• Primary Completion: December 16, 2022
• Study Completion: December 16, 2022
• Last Updated: February 23, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); US (6); CA (3)