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).
Brief Title
Open-Label, Dose-Escalation Study of Pemigatinib in Subjects With Advanced Malignancies - (FIGHT-101)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Lung Cancer
Solid Tumor
Gastric Cancer
Urothelial Cancer
Endometrial Cancer
Multiple Myeloma
Myeloproliferative Neoplasms
Breast Cancer
Cholangiocarcinoma
UC
MPN
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
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
Inclusion 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
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
Gender
All
Gender Based
false
Keywords
alterations in FGF or FGFR
squamous non-small cell lung cancer
gastric cancer
urothelial cancer
endometrial cancer
multiple myeloma
MPN
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02393248
Org Class
Industry
Org Full Name
Incyte Corporation
Org Study Id
INCB 54828-101
Overall Status
Terminated
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB054828 in Subjects With Advanced Malignancies (FIGHT-101)
Primary Outcomes
Outcome Description
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.
Outcome Measure
Parts 1 and 2 Combined: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
Outcome Time Frame
up to 763 days
Outcome Description
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.
Outcome Measure
Part 3: Number of Participants With Any TEAE
Outcome Time Frame
up to 869 days
Outcome Description
E0 was defined as the Baseline serum concentration of phosphate.
Outcome Measure
E0 Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2
Outcome Time Frame
predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles
Outcome Description
EC50 was defined as the pemigatinib steady-state area under the plasma or serum concentration-time curve that increases 50% of serum phosphate.
Outcome Measure
EC50 Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2
Outcome Time Frame
predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles
Outcome Description
Emax was defined as the maximum degree of increasing of serum phosphate by pemigatinib.
Outcome Measure
Emax Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2
Outcome Time Frame
predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles
Outcome Description
Serum phosphate concentration was assessed throughout Parts 1 and 2.
Outcome Measure
Highest Serum Phosphate Concentration Following Pemigatinib as Monotherapy in Parts 1 and 2
Outcome 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
Outcome Description
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.
Outcome Time Frame
up to 126 days
Outcome Measure
Part 2: Overall Response Rate (ORR)
Outcome Description
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.
Outcome Time Frame
up to 203 days
Outcome Measure
Part 3: ORR
Outcome Description
Cmax was defined as the maximum observed plasma concentration.
Outcome 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
Outcome Measure
Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1
Outcome Description
tmax was defined as the time to the maximum observed plasma concentration.
Outcome 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
Outcome Measure
Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1
Outcome Description
AUClast was defined as the area under the plasma or serum concentration-time curve from the time of dosing to the last measurable concentration.
Outcome 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
Outcome Measure
Parts 1 and 2: AUClast After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1
Outcome Description
AUC0-24 was defined as the area under the plasma or serum concentration-time curve from time 0 to 24 hours post-dose.
Outcome 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
Outcome Measure
Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1
Outcome Description
Cmax was defined as the maximum observed plasma concentration.
Outcome 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
Outcome Measure
Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
Outcome Description
tmax was defined as the time to the maximum observed plasma concentration.
Outcome 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
Outcome Measure
Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
Outcome Description
t1/2 was defined as the apparent plasma terminal phase disposition half-life.
Outcome 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
Outcome Measure
Parts 1 and 2: t1/2 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
Outcome Description
Cmin was defined as the minimum observed plasma concentration over the dose interval.
Outcome 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
Outcome Measure
Parts 1 and 2: Cmin After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
Outcome Description
AUC0-24 was defined as the area under the plasma or serum concentration-time curve from time 0 to 24 hours post-dose.
Outcome 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
Outcome Measure
Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
Outcome Description
CL/F was defined as the apparent oral dose clearance.
Outcome 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
Outcome Measure
Parts 1 and 2: CL/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
Outcome Description
Vz/F was defined as the apparent volume of distribution.
Outcome 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
Outcome Measure
Parts 1 and 2: Vz/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
Outcome Description
The accumulation ratio was defined as the ratio of the accumulation of a drug under steady-state conditions as compared to a single dose.
Outcome 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
Outcome Measure
Parts 1 and 2: Accumulation Ratio After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
Outcome Description
Cmax was defined as the maximum observed plasma concentration.
Outcome Time Frame
Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Outcome 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
Outcome Description
tmax was defined as the time to the maximum observed plasma concentration.
Outcome Time Frame
Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Outcome 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
Outcome Description
t1/2 was defined as the apparent plasma terminal phase disposition half-life.
Outcome Time Frame
Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Outcome 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
Outcome Description
Cmin was defined as the minimum observed plasma concentration over the dose interval.
Outcome Time Frame
Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Outcome 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
Outcome Description
AUC0-24 was defined as the area under the plasma or serum concentration-time curve from time 0 to 24 hours post-dose.
Outcome Time Frame
Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Outcome 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
Outcome Description
CL/F was defined as the apparent oral dose clearance.
Outcome Time Frame
Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Outcome 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
Outcome Description
Vz/F was defined as the apparent volume of distribution.
Outcome Time Frame
Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Outcome 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
Outcome Description
Cmax was defined as the maximum observed plasma concentration.
Outcome Time Frame
predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
Outcome Measure
Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1
Outcome Description
tmax was defined as the time to the maximum observed plasma concentration.
Outcome Time Frame
predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
Outcome Measure
Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1
Outcome Description
AUClast was defined as the area under the plasma or serum concentration-time curve from the time of dosing to the last measurable concentration.
Outcome Time Frame
predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
Outcome Measure
Part 3: AUClast of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1
Outcome Description
AUC0-24 was defined as the area under the plasma or serum concentration-time curve from time 0 to 24 hours post-dose.
Outcome Time Frame
predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
Outcome Measure
Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1
Outcome Description
Cmax was defined as the maximum observed plasma concentration.
Outcome Time Frame
predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Outcome Measure
Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
Outcome Description
tmax was defined as the time to the maximum observed plasma concentration.
Outcome Time Frame
predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Outcome Measure
Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
Outcome Description
t1/2 was defined as the apparent plasma terminal phase disposition half-life.
Outcome Time Frame
predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Outcome Measure
Part 3: t1/2 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
Outcome Description
Cmin was defined as the minimum observed plasma concentration over the dose interval.
Outcome Time Frame
predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Outcome Measure
Part 3: Cmin of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
Outcome Description
AUC0-24 was defined as the area under the plasma or serum concentration-time curve from time 0 to 24 hours post-dose.
Outcome Time Frame
predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Outcome Measure
Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
Outcome Description
CL/F was defined as the apparent oral dose clearance.
Outcome Time Frame
predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Outcome Measure
Part 3: CL/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
Outcome Description
Vz/F was defined as the apparent volume of distribution.
Outcome Time Frame
predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Outcome Measure
Part 3: Vz/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
Outcome Description
The accumulation ratio was defined as the ratio of the accumulation of a drug under steady-state conditions as compared to a single dose.
Outcome Time Frame
predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Outcome Measure
Part 3: Accumulation Ratio of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sanjay Goel
Investigator Email
sgoel@montefiore.org
Investigator Phone
718-405-8404