Efficacy and Safety of Pemigatinib in Previously Treated Locally Advanced/Metastatic or Surgically Unresectable Solid Tumor Malignancies Harboring Activating FGFR Mutations or Translocations (FIGHT-207)

Solid Tumor Malignancy Clinical Trial

Official title:

A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants With Previously Treated Locally Advanced/Metastatic or Surgically Unresectable Solid Tumor Malignancies Harboring Activating FGFR Mutations or Translocations (FIGHT-207)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03822117
• Other study ID #: INCB 54828-207
• Status: Terminated
• Phase: Phase 2
• Start date: October 17, 2019
• Est. completion date: March 29, 2022

Study information

• Verified date: March 2023
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of pemigatinib in participants with previously treated locally advanced/metastatic or surgically unresectable solid tumor malignancies harboring activating FGFR mutations or translocations.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 111
• Est. completion date: March 29, 2022
• Est. primary completion date: March 29, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed solid tumor malignancy that is advanced or metastatic or is surgically unresectable.
• Radiographically measurable disease (per RECIST v1.1 or RANO for primary brain tumors). Tumor lesions located in a previously irradiated area or in an area subjected to other loco-regional therapy are considered measureable if progression has been clearly demonstrated in the lesion.
• Documentation of an FGFR1-3 gene mutation or translocation.
• Objective progression after at least 1 prior therapy and no therapy available that is likely to provide clinical benefit. Participants who are intolerant to or decline the approved therapy are eligible only if they have no therapy available that is likely to provide clinical benefit.
• Eastern Cooperative Oncology Group performance status 0 to 2.
• Baseline archival tumor specimen (if less than 24 months from date of screening) or willingness to undergo a pretreatment tumor biopsy to obtain the specimen. Must be a tumor block or approximately 15 unstained slides from biopsy or resection of primary tumor or metastasis.
• Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

• Prior receipt of a selective FGFR inhibitor in the past 6 months.
• Receipt of anticancer medications or investigational drugs for any indication or reason within 28 days before first dose of pemigatinib.
• Cannot be a candidate for potentially curative surgery.
• Current evidence of clinically significant corneal or retinal disorder as confirmed by ophthalmologic examination.
• Radiation therapy administered within 2 weeks of enrollment/first dose of study treatment.
• Untreated brain or central nervous system (CNS) metastases or brain or CNS metastases that have progressed (eg, evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain or CNS metastases).
• Known additional malignancy that is progressing or requires active treatment.
• History of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues.
• Clinically significant or uncontrolled cardiac disease.
• Active chronic or current infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment within 2 weeks before enrollment (participants with asymptomatic chronic infections on prophylactic treatment are allowed).
• Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (defined as elevated transaminases or cirrhosis; chronic HBV/HCV infection with no cirrhosis and no elevated transaminases is allowed).
• Known HIV infection.
• Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14 days or five half-lives (whichever is longer) before the first dose of study drug/treatment.
• Women who are pregnant or breastfeeding.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor Malignancy

Intervention

Drug:
• Pemigatinib
Pemigatinib administered orally once daily (QD).

Locations

Country	Name	City	State
Denmark	The Finsen Centre National Hospital	Copenhagen
France	Institut Bergonie	Bordeaux
France	CENTRE GEORGES FRAN�OIS LECLERC	Dijon Cedex
France	Centre Antoine Lacassagne	Nice
France	A.P.H. Paris Hopital Cochin	Paris
France	Hospital Saint Louis	Paris
France	Institut Universitaire Du Cancer de Toulouse Oncopole	Toulouse
Germany	University Medical Center Freiburg	Freiburg
Germany	University Medical Centre Hamburg-Eppendorf, Centre of Oncology	Hamburg
Germany	Universitatsklinikum Koln	Koln
Germany	University Hospital Grosshadern Munich	Munich
Germany	Universitaetsklinikum in Tubingen	Tubingen
Israel	Ha Emek Medical Center	Afula
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah Hebrew University Medical Center Ein Karem Hadassah	Jerusalem
Israel	Rabin Medical Center - Beilinson Hospital	Petach Tikva
Israel	Assaf Harofeh Medical Center	Zerifin
Italy	L AZIENDA OSPEDALIERO-UNIVERSITARIA DI BOLOGNA POLICLINICO S. ORSOLA � MALPIGHI	Bologna
Italy	Fondazione Del Piemonte Per L Oncologia Ircc Candiolo	Candiolo
Italy	Fondazione Irccs Istituto Nazionale Dei Tumori	Milan
Italy	Istituto Nazionale Tumori Irccs Fondazione Pascale	Napoli
Italy	Istituto Nazionale Tumori Regina Elena Irccs	Roma
Italy	Centro Ricerche Cliniche Di Verona (Crc)	Verona
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	Kanazawa University Hospital	Ishikawa
Japan	Kobe University Hospital	Kobe
Japan	Tohoku University Hospital	Sendai-shi
Japan	Keio University Hospital	Shinjuku-ku
Japan	Shizuoka Cancer Center	Shizuoka
Japan	Kanagawa Cancer Center	Yokohama-shi
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Spain	Hospital Clinic I Provincial	Barcelona
Spain	Hospital General Universitario Vall D Hebron	Barcelona
Spain	Centro Integral Oncologico Clara Campal (Ciocc)	Madrid
Spain	Hospital Regional Universitario de Malaga	Malaga
Spain	Clinica Universidad de Navarra (Cun)	Pamplona
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Universitario Y Politcnico de La Fe	Valencia
Switzerland	Inselspital - Universitaetsspital Bern	Bern
Switzerland	Universitatsspital Zurich	Zuerich
United Kingdom	Imperial College Healthcare Nhs Trust - Hammersmith Hospital	London
United Kingdom	Sarah Cannon Research Institute	London
United Kingdom	University College London Hospitals (Uclh)	London
United States	Illinois Cancer Specialists	Arlington Heights	Illinois
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Oncology Specialists of Charlotte	Charlotte	North Carolina
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke Cancer Center	Durham	North Carolina
United States	Virginia Cancer Specialists, Pc	Fairfax	Virginia
United States	Summit Medical Group	Florham Park	New Jersey
United States	Florida Cancer Specialists & Research Institute	Fort Myers	Florida
United States	The West Clinic Pc	Germantown	Tennessee
United States	Cancer Treatment Centers of America	Goodyear	Arizona
United States	Cancer Institute of Greenville Health System	Greenville	South Carolina
United States	Houston Methodist Hospital	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	Indiana University Health - Arnett Cancer Care	Lafayette	Indiana
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Central Maine Medical Center	Lewiston	Maine
United States	Joe Arrington Cancer Center	Lubbock	Texas
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Winthrop University Hospital	Mineola	New York
United States	West Virginia University Hospitals Inc	Morgantown	West Virginia
United States	Ochsner Clinic	New Orleans	Louisiana
United States	Virginia Oncology Associates-Lake Wright	Norfolk	Virginia
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Chao Family Comprehensive Cancer Center University of California, Irvine	Orange	California
United States	Stanford Cancer Center	Palo Alto	California
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Florida Cancer Specialists	Saint Petersburg	Florida
United States	John Wayne Cancer Institute	Santa Monica	California
United States	St. Joseph Heritage Healthcare	Santa Rosa	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Edward H Kaplan & Associates	Skokie	Illinois
United States	Multicare Institute For Research & Innovation	Tacoma	Washington
United States	Florida Cancer Specialists	Tallahassee	Florida
United States	The University of Arizona Cancer Center	Tucson	Arizona
United States	Southwestern Regional Medical Center	Tulsa	Oklahoma
United States	Carle Cancer Center	Urbana	Illinois
United States	Florida Cancer Specialists	West Palm Beach	Florida
United States	University of Kansas Cancer Center	Westwood	Kansas
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina
United States	Umass Memorial Medical Center, Inc.	Worcester	Massachusetts
United States	Cancer Treatment Centers of America	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Denmark,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR), Defined as the Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) Based on RECIST v1.1 or RANO, in Participants With FGFR1-3 In-frame Fusions or FGFR2 Arrangements	Per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1): CR: disappearance of all target/non-target lesions; no appearance of new lesions. PR: complete disappearance or a =30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters; no new lesions; no progression of non-target lesions. Per Response Assessment in Neuro-Oncology (RANO; for participants with primary brain tumors): CR: disappearance of all enhancing lesions; stable/improved non-enhancing lesions; stable/improved clinically. PR: =50% decrease in sum of perpendicular diameters of measurable enhancing lesions; no progression of non-measurable disease; stable/improved non-enhancing lesions; stable/improved clinically. Cohort determination was based on FGFR status from a central genomics laboratory. Response data were from an independent centralized radiological review committee per RECIST v1.1 and RANO, and response was confirmed.	up to 483 days
Primary	ORR, Defined as the Percentage of Participants With a Best Overall Response of CR or PR Based on RECIST v1.1 or RANO, in Participants With Known or Likely Activating FGFR1-3 Mutations	Per RECIST v1.1: CR: disappearance of all target/non-target lesions; no appearance of new lesions. PR: complete disappearance or a =30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters; no new lesions; no progression of non-target lesions. Per RANO (for participants with primary brain tumors): CR: disappearance of all enhancing lesions; stable/improved non-enhancing lesions; stable/improved clinically. PR: =50% decrease in sum of perpendicular diameters of measurable enhancing lesions; no progression of non-measurable disease; stable/improved non-enhancing lesions; stable/improved clinically. Cohort determination was based on FGFR status from a central genomics laboratory. Response data were from an independent centralized radiological review committee per RECIST v1.1 and RANO, and response was confirmed.	up to 449 days
Secondary	Progression-free Survival (PFS) in Participants With FGFR1-3 In-frame Fusions or FGFR2 Arrangements and in Participants With Known or Likely Activating FGFR1-3 Mutations	PFS was defined as the time from the first dose until progressive disease (according to RECIST v1.1 or RANO for participants with primary brain tumors and assessed by an independent centralized radiological review committee) or death (whichever occurred first).	up to 532 days
Secondary	Duration of Response (DOR), Defined as the First CR or PR Assessment Until Progressive Disease (PD) or Death, in Participants With FGFR1-3 In-frame Fusions or FGFR2 Arrangements and in Participants With Known or Likely Activating FGFR1-3 Mutations	Assessment was by an independent centralized radiological review committee; response was confirmed. Per RECIST v1.1: CR: disappearance of all target (TLs)/non-target lesions (NTLs); no appearance of new lesions. PR: complete disappearance or a =30% decrease in the sum of the diameters of TLs, taking as a reference the baseline sum diameters; no new lesions; no progression of NTLs. PD: progression of a TL/NTL or presence of new lesion. Per RANO (participants with primary brain tumors): CR: disappearance of all enhancing lesions (ELs); stable/improved non-enhancing lesions (NELs); stable/improved clinically. PR: =50% decrease in sum of perpendicular diameters of measurable ELs; no progression of non-measurable disease; stable/improved NELs; stable/improved clinically. PD: >25% increase in sum of perpendicular diameters of all measurable ELs; significant increase of NELs; new lesions; clear clinical deterioration; failure to return for evaluation due to death/deteriorating condition.	up to 24.90 months
Secondary	Overall Survival in Participants With FGFR1-3 In-frame Fusions or FGFR2 Arrangements and in Participants With Known or Likely Activating FGFR1-3 Mutations	Overall survival was defined as the time from the first dose of study drug to death of any cause.	up to 532 days
Secondary	Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Treatment-related Adverse Event (AE)	An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. TEAEs were defined as AEs reported for the first time or the worsening of pre-existing events after the first dose of study treatment. Treatment-related AEs were defined as TEAEs judged as related by the investigator or with a missing causality.	up to 651 days