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

Helsinn Healthcare

Status and phase: Withdrawn; Phase 2; Phase 1

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

Treatments: Drug: Infigratinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05222165

INFI-21-07

2021-005614-34 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

Phase 1b:

Pediatric subjects with advanced solid and CNS tumors or recurrent or progressive Low-Grade Glioma with selected FGFR1-3 alterations will follow a standard dose escalation, in 3 dose levels, to determine the pediatric recommended Phase 2 dose (RP2D) and to assess the safety.

Dose escalation decisions will be assessed through three dose level cohorts.

Phase 2:

To evaluate the efficacy and safety in Pediatric and adult subjects with LGG with selected FGFR1-3 alterations (including subjects who received infigratinib at the RP2D).

Sex: All

Ages: 3+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Phase 1b:

• Subject must be ≥ 3 to <18 years of age at the Screening visit.

• Confirmed diagnosis of one of the following:

  1. 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
  2. Histologically/cytologically confirmed CNS tumor (other than LGG).
  3. 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

• Contraceptive and barrier use as well as pregnancy testing is required as appropriate for the age and sexual activity of pediatric and adult subjects and as required by local regulations.
• Subjects can be male and female.
• A legal guardian or caregiver must be able to accurately maintain the pediatric subject's take-home record, including items of general health.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 1 patient group

Infigratinib (BGJ398)

Experimental group

Description:

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.

Treatment:

Drug: Infigratinib