Clinical trial NCT02393248: Open-Label, Dose-Escalation Study of Pemigatinib in Subjects With Advanced Malignancies - (FIGHT-101)
Official title: A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB054828 in Subjects With Advanced Malignancies (FIGHT-101)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Lung Cancer
Solid Tumor
Gastric Cancer
Urothelial Cancer
Endometrial Cancer
Multiple Myeloma
Myeloproliferative Neoplasms
Breast Cancer
Cholangiocarcinoma
UC
MPN
Keywords: alterations in FGF or FGFR
squamous non-small cell lung cancer
gastric cancer
urothelial cancer
endometrial cancer
multiple myeloma
MPN
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2015-03-19
Enrollment: 201
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study will be to evaluate the safety, tolerability, and pharmacological activity of pemigatinib in subjects with advanced malignancies. This study will have three parts, dose escalation (Part 1), dose expansion (Part 2) and combination therapy (Part 3).


Eligibility criteria: Inclusion Criteria:

1. Male or female subjects, age 18 years or older on day of signing consent
2. Part 1: Any advanced solid tumor malignancy; Part 2: Subjects with squamous non-small cell lung cancer, cholangiocarcinoma/gastric cancer, urothelial cancer, breast/endometrial cancer, multiple myeloma, or MPNs that have a tumor or malignancy that has been evaluated and confirmed to harbor genetic alterations in FGF or FGFR genes. A subject's fibroblast growth factor (FGF) or fibroblast growth factor receptor (FGFR) alteration may be based on local or central laboratory results. Part 3: Dose finding: subjects with solid tumor malignancies who qualify for combo therapy; dose-expansion: FGF/FGFR+ subjects qualified to receive combo therapy
3. Has progressed after prior therapy and there is no further effective standard anticancer therapy available (including subject refuses or is intolerant)
4. Life expectancy \> 12 weeks
5. Eastern Cooperative Oncology Group (ECOG) performance status:

   * Part 1: 0 or 1
   * Part 2 and 3: 0, 1, or 2

Exclusion Criteria:

1. Treatment with other investigational study drug for any indication for any reason, or receipt of anticancer medications within 21 days or 5 half-lives before first dose of study drug
2. Prior receipt of a selective FGFR inhibitor
3. History of a calcium/phosphate homeostasis disorder
4. History and/or current evidence of ectopic mineralization/calcification
5. Current evidence of corneal disorder/keratopathy
6. Has a history or presence of inadequate liver, renal, hematopoietic and/or cardiac function parameters outside protocol-defined range
7. Prior radiotherapy within 2 weeks of study treatment

Primary outcomes:
measure: Parts 1 and 2 Combined: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
timeFrame: up to 763 days
measure: Part 3: Number of Participants With Any TEAE
timeFrame: up to 869 days
measure: E0 Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2
timeFrame: predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles
measure: EC50 Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2
timeFrame: predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles
measure: Emax Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2
timeFrame: predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles
measure: Highest Serum Phosphate Concentration Following Pemigatinib as Monotherapy in Parts 1 and 2
timeFrame: predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles
Secondary outcomes:
measure: Part 2: Overall Response Rate (ORR)
timeFrame: up to 126 days
measure: Part 3: ORR
timeFrame: up to 203 days
measure: Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1
timeFrame: Part 1: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose post-dose on Cycle 1 Day 1. Part 2: predose on Cycle 1 Day 1
measure: Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1
timeFrame: Part 1: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose post-dose on Cycle 1 Day 1. Part 2: predose on Cycle 1 Day 1
measure: Parts 1 and 2: AUClast After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1
timeFrame: Part 1: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose post-dose on Cycle 1 Day 1. Part 2: predose on Cycle 1 Day 1
measure: Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1
timeFrame: Part 1: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose post-dose on Cycle 1 Day 1. Part 2: predose on Cycle 1 Day 1
measure: Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
timeFrame: Part 1: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14. Part 2: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
measure: Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
timeFrame: Part 1: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14. Part 2: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
measure: Parts 1 and 2: t1/2 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
timeFrame: Part 1: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14. Part 2: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
measure: Parts 1 and 2: Cmin After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
timeFrame: Part 1: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14. Part 2: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
measure: Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
timeFrame: Part 1: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14. Part 2: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
measure: Parts 1 and 2: CL/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
timeFrame: Part 1: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14. Part 2: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
measure: Parts 1 and 2: Vz/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
timeFrame: Part 1: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14. Part 2: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
measure: Parts 1 and 2: Accumulation Ratio After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
timeFrame: Part 1: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14. Part 2: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
measure: Parts 1 and 2: Cmax Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States
timeFrame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
measure: Parts 1 and 2: Tmax Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States
timeFrame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
measure: Parts 1 and 2: t1/2 Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States
timeFrame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
measure: Parts 1 and 2: Cmin Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States
timeFrame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
measure: Parts 1 and 2: AUC0-24 Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States
timeFrame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
measure: Parts 1 and 2: CL/F Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States
timeFrame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
measure: Parts 1 and 2: Vz/F Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States
timeFrame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
measure: Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1
timeFrame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
measure: Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1
timeFrame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
measure: Part 3: AUClast of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1
timeFrame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
measure: Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1
timeFrame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
measure: Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
timeFrame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
measure: Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
timeFrame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
measure: Part 3: t1/2 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
timeFrame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
measure: Part 3: Cmin of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
timeFrame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
measure: Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
timeFrame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
measure: Part 3: CL/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
timeFrame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
measure: Part 3: Vz/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
timeFrame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
measure: Part 3: Accumulation Ratio of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
timeFrame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama At Birmingham Comprehensive Cancer Center
state: Alabama
city: West Hollywood
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Port Saint Lucie
country: United States
facility: Hematology Oncology Associates of the Tr
state: Florida
city: Atlanta
country: United States
facility: Emory University - Winship Cancer Institute
state: Georgia
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: John Theurer Cancer Center, Hackensack University Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New Hyde Park
country: United States
facility: Northwell Health - Monter Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University - Wexner Medical Center
state: Ohio
city: Middletown
country: United States
facility: Signal Point Clinical Research Center
state: Ohio
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute
state: South Carolina
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Ctr
state: Texas
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
city: Temple
country: United States
facility: Baylor Scott & White Health
state: Texas
city: Copenhagen
country: Denmark
facility: The Finsen Centre National Hospital
Study officials:
affiliation: Incyte Corporation
name: Luis Féliz, MD
role: STUDY_DIRECTOR
References:
citation: Subbiah V, Iannotti NO, Gutierrez M, Smith DC, Feliz L, Lihou CF, Tian C, Silverman IM, Ji T, Saleh M. FIGHT-101, a first-in-human study of potent and selective FGFR 1-3 inhibitor pemigatinib in pan-cancer patients with FGF/FGFR alterations and advanced malignancies. Ann Oncol. 2022 May;33(5):522-533. doi: 10.1016/j.annonc.2022.02.001. Epub 2022 Feb 14.
citation: Gong X, Ji T, Liu X, Chen X, Yeleswaram S. Evaluation of the clinical cardiac safety of pemigatinib, a fibroblast growth factor receptor inhibitor, in participants with advanced malignancies. Pharmacol Res Perspect. 2022 Feb;10(1):e00906. doi: 10.1002/prp2.906.