Open-Label, Dose-Escalation Study of Pemigatinib in Subjects With Advanced Malignancies - (FIGHT-101)

Phase 2TerminatedNCT02393248

Incyte Corporation201 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

201

Conditions

Lung Cancer Solid Tumor Gastric Cancer Urothelial Cancer Endometrial Cancer Multiple Myeloma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (20)

University of Alabama At Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States

Cedars-Sinai Medical Center

West Hollywood, California, United States

Yale Cancer Center

New Haven, Connecticut, United States

Georgetown University Hospital

Washington D.C., District of Columbia, United States

Hematology Oncology Associates of the Tr

Port Saint Lucie, Florida, United States

Emory University - Winship Cancer Institute

Atlanta, Georgia, United States

University of Michigan Health System

Ann Arbor, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

John Theurer Cancer Center, Hackensack University Medical Center

Hackensack, New Jersey, United States

Northwell Health - Monter Cancer Center

New Hyde Park, New York, United States

...and 10 more locations

Outcomes

Primary Outcomes

Parts 1 and 2 Combined: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)

Adverse events were defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occurred after a participant provided informed consent. Abnormal laboratory values or test results that occurred after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). TEAEs were defined as adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last dose of study drug.

Time frame: up to 763 days

Part 3: Number of Participants With Any TEAE

Time frame: up to 869 days

E0 Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2

E0 was defined as the Baseline serum concentration of phosphate.

Time frame: predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles

EC50 Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2

EC50 was defined as the pemigatinib steady-state area under the plasma or serum concentration-time curve that increases 50% of serum phosphate.

Time frame: predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles

Emax Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2

Emax was defined as the maximum degree of increasing of serum phosphate by pemigatinib.

Time frame: predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles

Highest Serum Phosphate Concentration Following Pemigatinib as Monotherapy in Parts 1 and 2

Serum phosphate concentration was assessed throughout Parts 1 and 2.

Time frame: predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles

Secondary Outcomes

Part 2: Overall Response Rate (ORR)

ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as determined by the investigator. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.

Time frame: up to 126 days

Part 3: ORR

ORR was defined as the percentage of participants with a best overall response of CR or PR, per RECIST version 1.1, as determined by the investigator. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.

Time frame: up to 203 days

Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1

Cmax was defined as the maximum observed plasma concentration.

Time frame: 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

Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1

tmax was defined as the time to the maximum observed plasma concentration.

Time frame: 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

Parts 1 and 2: AUClast After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1

AUClast was defined as the area under the plasma or serum concentration-time curve from the time of dosing to the last measurable concentration.

Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1

AUC0-24 was defined as the area under the plasma or serum concentration-time curve from time 0 to 24 hours post-dose.

Time frame: 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

Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)

Cmax was defined as the maximum observed plasma concentration.

Time frame: 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

Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)

tmax was defined as the time to the maximum observed plasma concentration.

Parts 1 and 2: t1/2 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)

t1/2 was defined as the apparent plasma terminal phase disposition half-life.

Parts 1 and 2: Cmin After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)

Cmin was defined as the minimum observed plasma concentration over the dose interval.

Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)

AUC0-24 was defined as the area under the plasma or serum concentration-time curve from time 0 to 24 hours post-dose.

Parts 1 and 2: CL/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)

CL/F was defined as the apparent oral dose clearance.

Parts 1 and 2: Vz/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)

Vz/F was defined as the apparent volume of distribution.

Parts 1 and 2: Accumulation Ratio After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)

The accumulation ratio was defined as the ratio of the accumulation of a drug under steady-state conditions as compared to a single dose.

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

Cmax was defined as the maximum observed plasma concentration.

Time frame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14

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

tmax was defined as the time to the maximum observed plasma concentration.

Time frame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14

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

t1/2 was defined as the apparent plasma terminal phase disposition half-life.

Time frame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14

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

Cmin was defined as the minimum observed plasma concentration over the dose interval.

Time frame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14

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

AUC0-24 was defined as the area under the plasma or serum concentration-time curve from time 0 to 24 hours post-dose.

Time frame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14

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

CL/F was defined as the apparent oral dose clearance.

Time frame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14

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

Vz/F was defined as the apparent volume of distribution.

Time frame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14

Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1

Cmax was defined as the maximum observed plasma concentration.

Time frame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1

Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1

tmax was defined as the time to the maximum observed plasma concentration.

Time frame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1

Part 3: AUClast of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1

AUClast was defined as the area under the plasma or serum concentration-time curve from the time of dosing to the last measurable concentration.

Time frame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1

Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1

AUC0-24 was defined as the area under the plasma or serum concentration-time curve from time 0 to 24 hours post-dose.

Time frame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1

Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)

Cmax was defined as the maximum observed plasma concentration.