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

Breast Cancer Clinical Trial

Official title:

A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB054828 in Subjects With Advanced Malignancies (FIGHT-101)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02393248
• Other study ID #: INCB 54828-101
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: February 27, 2015
• Est. completion date: December 17, 2021

Study information

• Verified date: December 2022
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 201
• Est. completion date: December 17, 2021
• Est. primary completion date: December 17, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Cholangiocarcinoma
• Endometrial Cancer
• Endometrial Neoplasms
• Gastric Cancer
• Lung Cancer
• MPN
• Multiple Myeloma
• Myeloproliferative Disorders
• Myeloproliferative Neoplasms
• Solid Tumor
• Stomach Neoplasms
• UC
• Urothelial Cancer

Intervention

Drug:
• Pemigatinib

• Gemcitabine

• Pembrolizumab

• Docetaxel

• Trastuzumab

• Retifanlimab

• Cisplatin

Locations

Country	Name	City	State
Denmark	The Finsen Centre National Hospital	Copenhagen
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Emory University - Winship Cancer Institute	Atlanta	Georgia
United States	University of Alabama At Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Montefiore Medical Center	Bronx	New York
United States	Ohio State University - Wexner Medical Center	Columbus	Ohio
United States	Mary Crowley Cancer Research Ctr	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Greenville Health System Cancer Institute	Greenville	South Carolina
United States	John Theurer Cancer Center, Hackensack University Medical Center	Hackensack	New Jersey
United States	Md Anderson Cancer Center	Houston	Texas
United States	Signal Point Clinical Research Center	Middletown	Ohio
United States	Yale Cancer Center	New Haven	Connecticut
United States	Northwell Health - Monter Cancer Center	New Hyde Park	New York
United States	Hematology Oncology Associates of the Tr	Port Saint Lucie	Florida
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	South Texas Accelerated Research Therapeutics	San Antonio	Texas
United States	Baylor Scott & White Health	Temple	Texas
United States	Georgetown University Hospital	Washington	District of Columbia
United States	Cedars-Sinai Medical Center	West Hollywood	California

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	up to 763 days
Primary	Part 3: Number of Participants With Any 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.	up to 869 days
Primary	E0 Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2	E0 was defined as the Baseline serum concentration of phosphate.	predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles
Primary	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.	predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles
Primary	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.	predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles
Primary	Highest Serum Phosphate Concentration Following Pemigatinib as Monotherapy in Parts 1 and 2	Serum phosphate concentration was assessed throughout Parts 1 and 2.	predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles
Secondary	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.	up to 126 days
Secondary	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.	up to 203 days
Secondary	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.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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.	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
Secondary	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.	Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Secondary	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.	Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Secondary	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.	Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Secondary	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.	Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Secondary	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.	Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Secondary	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.	Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Secondary	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.	Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Secondary	Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1	Cmax was defined as the maximum observed plasma concentration.	predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
Secondary	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.	predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
Secondary	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.	predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
Secondary	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.	predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
Secondary	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.	predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Secondary	Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)	tmax was defined as the time to the maximum observed plasma concentration.	predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Secondary	Part 3: t1/2 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)	t1/2 was defined as the apparent plasma terminal phase disposition half-life.	predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Secondary	Part 3: Cmin of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)	Cmin was defined as the minimum observed plasma concentration over the dose interval.	predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Secondary	Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 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.	predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Secondary	Part 3: CL/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)	CL/F was defined as the apparent oral dose clearance.	predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Secondary	Part 3: Vz/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)	Vz/F was defined as the apparent volume of distribution.	predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Secondary	Part 3: Accumulation Ratio of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 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.	predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14