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)
- Registration Number
- NCT03822117
- Lead Sponsor
- Incyte Corporation
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 111
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Pemigatinib Pemigatinib Cohort A (Solid tumor malignancies with FGFR1-3 in frame fusions; any FGFR2 rearrangement; FGFR1/3 rearrangement with known partner\*). Cohort B (Solid tumor malignancies with known or likely activating mutations (excluding kinase domain) in FGFR1-3) Cohort C (Solid tumor malignancies with FGFR1-3 known activating mutations in kinase domain; FGFR1-3 putatively activating mutations; other FGFR1/3 rearrangements\* (not eligible for Cohort A)). \*Only FGFR fusions or rearrangements with an intact kinase domain are eligible
- Primary Outcome Measures
Name Time Method 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 up to 449 days 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.
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 up to 483 days 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.
- Secondary Outcome Measures
Name Time Method 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 up to 532 days 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).
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 up to 24.90 months 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.
Overall Survival in Participants With FGFR1-3 In-frame Fusions or FGFR2 Arrangements and in Participants With Known or Likely Activating FGFR1-3 Mutations up to 532 days Overall survival was defined as the time from the first dose of study drug to death of any cause.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Treatment-related Adverse Event (AE) up to 651 days 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.
Trial Locations
- Locations (87)
Cancer Treatment Centers of America
🇺🇸Zion, Illinois, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
The University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
Chao Family Comprehensive Cancer Center University of California, Irvine
🇺🇸Orange, California, United States
Stanford Cancer Center
🇺🇸Palo Alto, California, United States
John Wayne Cancer Institute
🇺🇸Santa Monica, California, United States
St. Joseph Heritage Healthcare
🇺🇸Santa Rosa, California, United States
Florida Cancer Specialists & Research Institute
🇺🇸Fort Myers, Florida, United States
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
Florida Cancer Specialists
🇺🇸West Palm Beach, Florida, United States
Scroll for more (77 remaining)Cancer Treatment Centers of America🇺🇸Zion, Illinois, United States