Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants With Previously Treated Glioblastoma or Other Primary Central Nervous System Tumors Harboring Activating FGFR1-3 Alterations (FIGHT-209)

• ClinicalTrials.gov Identifier: NCT05267106
• Recruitment Status: Recruiting
• First Posted: March 4, 2022
• Last Update Posted: May 18, 2023
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

Tracking Information

• First Submitted Date: February 15, 2022
• First Posted Date: March 4, 2022
• Last Update Posted Date: May 18, 2023
• Actual Study Start Date: May 20, 2022
• Estimated Primary Completion Date: January 30, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 27, 2023)

Cohort A: Overall Response Rate (ORR) [ Time Frame: Up to 3 months ]

Defined as the proportion of participants in Cohort A who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Assessment in Neuro-Oncology (RANO) as determined by an Independent Central Radiology (ICR).

Original Primary Outcome Measures (submitted: February 23, 2022)

• Cohort A: Overall Response Rate (ORR) [ Time Frame: Up to 3 months ]
  Defined as the proportion of participants in Cohort A who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Assessment in Neuro-Oncology (RANO) as determined by an Independent Central Radiology (ICR).
• Cohort B: ORR [ Time Frame: Up to 3 months ]
  Defined as the proportion of participants who achieve a CR or PR based on RECIST v1.1. Response will be determined by an ICR review.

Current Secondary Outcome Measures (submitted: March 27, 2023)

• Cohort B : ORR [ Time Frame: up to 3 months ]
  Defined as the proportion of participants who achieve a CR or PR based on RANO. Response will be determined by an ICR review.
• Cohorts A and B combined: ORR [ Time Frame: Up to 3 months ]
  Defined as the proportion of participants in Cohorts A and B who achieve a BOR of CR or PR based on RANO as determined by an ICR.
• Cohorts A and B: Disease Control Rate (DCR) [ Time Frame: Up to 3 months ]
  Defined as the proportion of participants who achieve a CR, PR, or SD as assessed by ICR in cohorts A and B respectively
• Cohorts A and B: Progression-Free Survival (PFS) [ Time Frame: Up to 3 months ]
  Defined as the time from first dose until progressive disease (according to RANO and assessed by an ICR) or death (whichever occurs first) in cohorts A and B, respectively
• Cohorts A and B: Overall Survival (OS) [ Time Frame: Up to 3 months ]
  Defined as the time from first dose of study drug to death due to any cause in cohorts A and B respectively
• Safety and tolerability [ Time Frame: Up to 3 months ]
  Safety and tolerability in each cohort, assessed by monitoring the frequency and severity of AEs according to NCICTCAE v5.0.
• Cohorts A and B : Duration Of Response (DOR) [ Time Frame: up to 3 months ]
  Defined as the time from first assessment of Complete Response (CR) or Partial Response (PR) until progressive disease (according to RANO and assessed by an ICR), or death (whichever occurs first) in cohorts A and B, respectively

Original Secondary Outcome Measures (submitted: February 23, 2022)

• Cohorts A and B combined: ORR [ Time Frame: Up to 3 months ]
  defined as the proportion of participants in Cohorts A and B who achieve a BOR of CR or PR based on RANO as determined by an ICR.
• Cohorts A, B, and C combined: ORR [ Time Frame: Up to 3 months ]
  defined as the proportion of participants in Cohorts A, B, and C combined who achieve a BOR of CR or PR based on RANO as determined by an ICR.
• Cohort C: ORR [ Time Frame: Up to 3 months ]
  defined as the proportion of participants in Cohort C who achieve a BOR of CR or PR based on RANO as determined by an ICR.
• Cohorts A, B and C: ORR [ Time Frame: Up to 3 months ]
  proportion of participants in each cohort who achieve a BOR of CR or PR based on RANO as determined by investigator assessment
• Cohorts A and B: Disease Control Rate (DCR) [ Time Frame: Up to 3 months ]
  described as the proportion of participants who achieve a CR, PR, or SD as assessed by ICR.
• Cohorts A and B: Progression-Free Survival (PFS) [ Time Frame: Up to 3 months ]
  defined as the time from first dose until progressive disease (according to RANO and assessed by an ICR) or death (whichever occurs first).
• Cohorts A and B: Duration of Response (DOR) [ Time Frame: Up to 3 months ]
  defined as the time from the date of first assessment of CR or PR until the date of the first progressive disease (according to RANO and assessed by an ICR), or death (whichever is first).
• Cohorts A and B: Overall Survival (OS) [ Time Frame: Up to 3 months ]
  defined as the time from first dose of study drug to death of any cause.
• Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 3 months ]
  TEAE is any Adverse Event (AE) either reported for the first time or worsening of a pre-existing event after first dose of study drug.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants With Previously Treated Glioblastoma or Other Primary Central Nervous System Tumors Harboring Activating FGFR1-3 Alterations
• Official Title: A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants With Previously Treated Glioblastoma or Other Primary Central Nervous System Tumors Harboring Activating FGFR1-3 Alterations (FIGHT-209)
• Brief Summary: This is an open-label, monotherapy study of pemigatinib in participants with recurrent glioblastoma (GBM) or other recurrent gliomas, circumscribed astrocytic gliomas, and glioneuronal and neuronal tumors with an activating FGFR1-3 mutation or fusion/rearrangement. This study consists of 2 cohorts, Cohorts A, and B, and will enroll approximately 82 participants into each cohort. Participants will receive pemigatinib 13.5 mg QD on a 2-week on-therapy and 1-week off-therapy schedule as long as they are receiving benefit and have not met any criteria for study withdrawal.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This study consists of 2 cohorts and participants will receive pemigatinib 13.5 mg QD on a 2-week on-therapy and 1-week off-therapy schedule.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Glioblastoma
• Adult-type Diffuse Gliomas

Intervention

Drug: Pemigatinib

13.5mg tablet taken every morning (unless otherwise directed) for 2 weeks and then 1 week off.

Other Name: NCB054828

Study Arms

• Experimental: Cohort A: IDH-wild-type GBM
  Participants with histopathologically proven, WHO Grade 4, IDH-wild-type GBM OR molecular diagnosis of IDH-wild-type, diffuse astrocytic glioma with molecular features of Grade 4 GBM that are recurrent, harboring FGFR1-3 fusions/or other rearrangements, or with a defined FGFR1-3 mutation or in-frame deletion.
  Intervention: Drug: Pemigatinib
• Experimental: Cohort B: Other gliomas other than GBM
  Participants with other histopathologically proven gliomas other than GBM, circumscribed astrocytic gliomas, and glioneuronal and neuronal tumors that are recurrent, harboring FGFR1-3 fusions/or other rearrangements or with a defined FGFR1-3 activating mutation or in-frame deletion
  Intervention: Drug: Pemigatinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 27, 2023): 164
• Original Estimated Enrollment (submitted: February 23, 2022): 189
• Estimated Study Completion Date: January 30, 2026
• Estimated Primary Completion Date: January 30, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histological, cytological, or molecular confirmation of recurrent GBM or other glioma, circumscribed astrocytic glioma, or glioneuronalor neuronal tumors that has recurred.

• Radiographically measurable disease.

  . -Karnofsky performance status ≥ 60.

• Life expectancy ≥ 12 weeks.
• Documentation of an actionable FGFR1-3 gene mutation or fusion/rearrangement from tissue : FGFR1-3 fusions or other rearrangements (FGFR1-3 in-frame fusions, any FGFR2 rearrangement, or FGFR1/3 rearrangement with known partner) or a defined FGFR1-3 activating mutation or in-frame deletion. Only participants with FGFR fusions or rearrangements with an intact kinase domain are eligible.
• MRI-documented objective progression after prior therapy and must have no therapy available that is likely to provide clinical benefit.
• Most recent archival tumor specimen must be a tumor block or a minimum of 15 unstained slides from biopsy or resection of primary tumor or metastasis.
• Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

• Prior receipt of an FGFR inhibitor.
• Receipt of anticancer medications or investigational drugs for any indication or reason within 28 days before first dose of study drug.
• Participants may have had treatment for an unlimited number of prior relapses but must not have had prior bevacizumab or other VEGF/VEGFR inhibitors (exception: prior bevacizumab is allowed if it was administered for the treatment of radiation necrosis rather than progressive tumor and was stopped at least 12 weeks prior to MRI showing tumor progression).
• Concurrent anticancer therapy
• Candidate for potentially curative surgery.
• Dexamethasone (or equivalent) > 4 mg daily at the time of study registration
• Current evidence of clinically significant corneal or retinal disorder as confirmed by ophthalmologic examination.
• Diffuse leptomeningeal disease.
• Radiation therapy administered within 12 weeks before enrollment/first dose of study drug.
• Known additional malignancy that is progressing or requires active systemic treatment.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Incyte Corporation Call Center (US); 1.855.463.3463; medinfo@incyte.com

Contact: Incyte Corporation Call Center (ex-US); +800 00027423; eumedinfo@incyte.com

• Listed Location Countries: Denmark, France, Germany, Italy, Japan, Netherlands, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05267106
• Other Study ID Numbers: INCB 54828-209
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• URL: https://www.incyte.com/our-company/compliance-and-transparency

• Current Responsible Party: Incyte Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Incyte Corporation
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Victoria Ebiana, MD; Incyte Corporation

• PRS Account: Incyte Corporation
• Verification Date: May 2023