MedPath

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

Phase 1
Terminated
Conditions
UC
MPN
Lung Cancer
Solid Tumor
Gastric Cancer
Urothelial Cancer
Endometrial Cancer
Multiple Myeloma
Myeloproliferative Neoplasms
Breast Cancer
Interventions
Registration Number
NCT02393248
Lead Sponsor
Incyte Corporation
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
201
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Part 1: Intermittent pemigatinib 1/2/4 mg QDPemigatinibParticipants self-administered oral pemigatinib 1/2/4 milligrams (mg) once daily (QD) on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break.
Part 1: Intermittent pemigatinib 6 mg QDPemigatinibParticipants self-administered oral pemigatinib 6 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break.
Part 1: Intermittent pemigatinib 9 mg QDPemigatinibParticipants self-administered oral pemigatinib 9 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break.
Part 1: Intermittent pemigatinib 13.5 mg QDPemigatinibParticipants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break.
Part 1: Intermittent pemigatinib 20 mg QDPemigatinibParticipants self-administered oral pemigatinib 20 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break.
Part 1: Continuous pemigatinib 9 mg QDPemigatinibParticipants self-administered oral pemigatinib 9 mg QD on Days 1 through 21 of each 21-day cycle.
Part 1: Continuous pemigatinib 10 mg BIDPemigatinibParticipants self-administered oral pemigatinib 10 mg BID on Days 1 through 21 of each 21-day cycle.
Part 2: Intermittent pemigatinib 9 mg QDPemigatinibParticipants self-administered oral pemigatinib 9 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break.
Part 2: Intermittent pemigatinib 13.5 mg QDPemigatinibParticipants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break.
Part 2: Continuous pemigatinib 9 mg QDPemigatinibParticipants self-administered oral pemigatinib 9 mg QD on Days 1 through 21 of each 21-day cycle.
Part 2: Continuous pemigatinib 13.5 mg QDPemigatinibParticipants self-administered oral pemigatinib 13.5 mg QD on Days 1 through 21 of each 21-day cycle.
Part 2: Continuous pemigatinib 20 mg QDPemigatinibParticipants self-administered oral pemigatinib 20 mg QD on Days 1 through 21 of each 21-day cycle.
Part 3: Gem/Cis/intermittent pemigatinib 9 mgCisplatinParticipants received gemcitabine (Gem) intravenously starting at 1000 mg/meters squared (m\^2) (30 minutes) on Days 1 and 8 of each 21-day cycle. Cisplatin (Cis) was administered intravenously starting at 70 mg/m\^2 (1-4 hours) once every 3 weeks on Day 1 of each 21-day cycle. Both gemcitabine and cisplatin doses could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued chemotherapy with medical monitor approval. Participants self-administered oral pemigatinib 9 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of gemcitabine/cisplatin.
Part 3: Doc/intermittent pemigatinib 13.5 mgDocetaxelParticipants received docetaxel (Doc) intravenously starting at 75 mg/m\^2 (1 hour) once every 3 weeks on Day 1 of each cycle. The dose could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued chemotherapy with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of docetaxel.
Part 3: Pem/intermittent pemigatinib 9 mgPembrolizumabParticipants received pembrolizumab (Pem) intravenously at 200 mg (30 minutes) once every 3 weeks on Day 1 of each cycle. The dose could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued pembrolizumab with medical monitor approval. Participants self-administered oral pemigatinib 9 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of pembrolizumab.
Part 3: Pem/intermittent pemigatinib 13.5 mgPembrolizumabParticipants received pembrolizumab intravenously at 200 mg (30 minutes) once every 3 weeks on Day 1 of each cycle. The dose could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued pembrolizumab with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of pembrolizumab.
Part 3: Pem/continuous pemigatinib 13.5 mgPembrolizumabParticipants received pembrolizumab intravenously at 200 mg (30 minutes) once every 3 weeks on Day 1 of each cycle. The dose could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued pembrolizumab with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on Days 1 through 21 of each 21-day cycle. It was permissible to continue pemigatinib administration during the toxicity break of pembrolizumab.
Part 1: Continuous pemigatinib 13.5 mg QDPemigatinibParticipants self-administered oral pemigatinib 13.5 mg QD on Days 1 through 21 of each 21-day cycle.
Part 1: Continuous pemigatinib 20 mg QDPemigatinibParticipants self-administered oral pemigatinib 20 mg QD on Days 1 through 21 of each 21-day cycle.
Part 1: Continuous pemigatinib 7.5 mg BIDPemigatinibParticipants self-administered oral pemigatinib 7.5 mg twice daily (BID) on Days 1 through 21 of each 21-day cycle.
Part 3: Gem/Cis/intermittent pemigatinib 9 mgPemigatinibParticipants received gemcitabine (Gem) intravenously starting at 1000 mg/meters squared (m\^2) (30 minutes) on Days 1 and 8 of each 21-day cycle. Cisplatin (Cis) was administered intravenously starting at 70 mg/m\^2 (1-4 hours) once every 3 weeks on Day 1 of each 21-day cycle. Both gemcitabine and cisplatin doses could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued chemotherapy with medical monitor approval. Participants self-administered oral pemigatinib 9 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of gemcitabine/cisplatin.
Part 3: Gem/Cis/intermittent pemigatinib 9 mgGemcitabineParticipants received gemcitabine (Gem) intravenously starting at 1000 mg/meters squared (m\^2) (30 minutes) on Days 1 and 8 of each 21-day cycle. Cisplatin (Cis) was administered intravenously starting at 70 mg/m\^2 (1-4 hours) once every 3 weeks on Day 1 of each 21-day cycle. Both gemcitabine and cisplatin doses could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued chemotherapy with medical monitor approval. Participants self-administered oral pemigatinib 9 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of gemcitabine/cisplatin.
Part 3: Gem/Cis/intermittent pemigatinib 13.5 mgPemigatinibParticipants received gemcitabine intravenously starting at 1000 mg/m\^2 (30 minutes) on Days 1 and 8 of each 21-day cycle. Cisplatin was administered intravenously starting at 70 mg/m\^2 (1-4 hours) once every 3 weeks on Day 1 of each 21-day cycle. Both gemcitabine and cisplatin doses could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued chemotherapy with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of gemcitabine/cisplatin.
Part 3: Gem/Cis/intermittent pemigatinib 13.5 mgGemcitabineParticipants received gemcitabine intravenously starting at 1000 mg/m\^2 (30 minutes) on Days 1 and 8 of each 21-day cycle. Cisplatin was administered intravenously starting at 70 mg/m\^2 (1-4 hours) once every 3 weeks on Day 1 of each 21-day cycle. Both gemcitabine and cisplatin doses could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued chemotherapy with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of gemcitabine/cisplatin.
Part 3: Gem/Cis/intermittent pemigatinib 13.5 mgCisplatinParticipants received gemcitabine intravenously starting at 1000 mg/m\^2 (30 minutes) on Days 1 and 8 of each 21-day cycle. Cisplatin was administered intravenously starting at 70 mg/m\^2 (1-4 hours) once every 3 weeks on Day 1 of each 21-day cycle. Both gemcitabine and cisplatin doses could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued chemotherapy with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of gemcitabine/cisplatin.
Part 3: Tras/intermittent pemigatinib 13.5 mgPemigatinibTrastuzumab (Tras) was administered as an open-label, commercial product at an initial dose of 8 mg/kilograms (kg) over a 90-minute intravenous infusion, followed by 6 mg/kg over a 30- to 90-minute intravenous infusion once every 3 weeks. The dose could have been adjusted for toxicity management, per commercial labeling. The investigator could have interrupted, modified, or discontinued trastuzumab with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of trastuzumab.
Part 3: Doc/intermittent pemigatinib 13.5 mgPemigatinibParticipants received docetaxel (Doc) intravenously starting at 75 mg/m\^2 (1 hour) once every 3 weeks on Day 1 of each cycle. The dose could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued chemotherapy with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of docetaxel.
Part 3: Tras/intermittent pemigatinib 13.5 mgTrastuzumabTrastuzumab (Tras) was administered as an open-label, commercial product at an initial dose of 8 mg/kilograms (kg) over a 90-minute intravenous infusion, followed by 6 mg/kg over a 30- to 90-minute intravenous infusion once every 3 weeks. The dose could have been adjusted for toxicity management, per commercial labeling. The investigator could have interrupted, modified, or discontinued trastuzumab with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of trastuzumab.
Part 3: Pem/intermittent pemigatinib 9 mgPemigatinibParticipants received pembrolizumab (Pem) intravenously at 200 mg (30 minutes) once every 3 weeks on Day 1 of each cycle. The dose could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued pembrolizumab with medical monitor approval. Participants self-administered oral pemigatinib 9 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of pembrolizumab.
Part 3: Pem/intermittent pemigatinib 13.5 mgPemigatinibParticipants received pembrolizumab intravenously at 200 mg (30 minutes) once every 3 weeks on Day 1 of each cycle. The dose could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued pembrolizumab with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of pembrolizumab.
Part 3: Pem/continuous pemigatinib 13.5 mgPemigatinibParticipants received pembrolizumab intravenously at 200 mg (30 minutes) once every 3 weeks on Day 1 of each cycle. The dose could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued pembrolizumab with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on Days 1 through 21 of each 21-day cycle. It was permissible to continue pemigatinib administration during the toxicity break of pembrolizumab.
Part 3: Ref/continuous pemigatinib 9 mgPemigatinibRetifanlimab (Ref) was administered once every 4 weeks on a 28-day cycle as an open-label product, at an initial dose of 500 mg over a 60-minute intravenous infusion. Participants self-administered oral pemigatinib 9 mg QD on Days 1 through 21 of each 21-day cycle.
Part 3: Ref/continuous pemigatinib 9 mgRetifanlimabRetifanlimab (Ref) was administered once every 4 weeks on a 28-day cycle as an open-label product, at an initial dose of 500 mg over a 60-minute intravenous infusion. Participants self-administered oral pemigatinib 9 mg QD on Days 1 through 21 of each 21-day cycle.
Part 3: Ref/continuous pemigatinib 20 mgPemigatinibRetifanlimab was administered once every 4 weeks on a 28-day cycle as an open-label product, at an initial dose of 500 mg over a 60-minute intravenous infusion. Participants self-administered oral pemigatinib 20 mg QD on Days 1 through 21 of each 21-day cycle.
Part 3: Ref/continuous pemigatinib 13.5 mgPemigatinibRetifanlimab was administered once every 4 weeks on a 28-day cycle as an open-label product, at an initial dose of 500 mg over a 60-minute intravenous infusion. Participants self-administered oral pemigatinib 13.5 mg QD on Days 1 through 21 of each 21-day cycle.
Part 3: Ref/continuous pemigatinib 13.5 mgRetifanlimabRetifanlimab was administered once every 4 weeks on a 28-day cycle as an open-label product, at an initial dose of 500 mg over a 60-minute intravenous infusion. Participants self-administered oral pemigatinib 13.5 mg QD on Days 1 through 21 of each 21-day cycle.
Part 3: Ref/continuous pemigatinib 20 mgRetifanlimabRetifanlimab was administered once every 4 weeks on a 28-day cycle as an open-label product, at an initial dose of 500 mg over a 60-minute intravenous infusion. Participants self-administered oral pemigatinib 20 mg QD on Days 1 through 21 of each 21-day cycle.
Primary Outcome Measures
NameTimeMethod
Parts 1 and 2 Combined: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)up to 763 days

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.

Part 3: Number of Participants With Any TEAEup to 869 days

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.

E0 Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles

E0 was defined as the Baseline serum concentration of phosphate.

EC50 Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles

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

Emax Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles

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

Highest Serum Phosphate Concentration Following Pemigatinib as Monotherapy in Parts 1 and 2predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles

Serum phosphate concentration was assessed throughout Parts 1 and 2.

Secondary Outcome Measures
NameTimeMethod
Part 2: Overall Response Rate (ORR)up to 126 days

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.

Part 3: ORRup to 203 days

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.

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

Cmax was defined as the maximum observed plasma concentration.

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

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

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

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 1Part 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

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

Cmax was defined as the maximum observed plasma concentration.

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

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)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

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)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

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)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

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)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

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)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

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

Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1

Cmax was defined as the maximum observed plasma concentration.

Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1

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

Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose 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 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14

Cmax was defined as the maximum observed plasma concentration.

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

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: Tmax Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) StatesCycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14

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

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) StatesCycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14

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

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) StatesCycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14

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

Parts 1 and 2: Cmax Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) StatesCycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14

Cmax was defined as the maximum observed plasma concentration.

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) StatesCycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14

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

Part 3: Cmin of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14

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

Parts 1 and 2: Cmin Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) StatesCycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14

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

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) StatesCycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14

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

Part 3: AUClast of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose 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 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14

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

Part 3: t1/2 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14

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

Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14

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

Part 3: CL/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14

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

Part 3: Vz/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14

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

Part 3: Accumulation Ratio of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14

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

Trial Locations

Locations (20)

Ohio State University - Wexner Medical Center

🇺🇸

Columbus, Ohio, United States

South Texas Accelerated Research Therapeutics

🇺🇸

San Antonio, Texas, United States

University of Michigan Health System

🇺🇸

Ann Arbor, Michigan, United States

University of Alabama At Birmingham Comprehensive Cancer Center

🇺🇸

Birmingham, Alabama, United States

Georgetown University Hospital

🇺🇸

Washington, District of Columbia, United States

Hematology Oncology Associates of the Tr

🇺🇸

Port Saint Lucie, Florida, United States

Cedars-Sinai Medical Center

🇺🇸

West Hollywood, California, United States

John Theurer Cancer Center, Hackensack University Medical Center

🇺🇸

Hackensack, New Jersey, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

Northwell Health - Monter Cancer Center

🇺🇸

New Hyde Park, New York, United States

The Finsen Centre National Hospital

🇩🇰

Copenhagen, Denmark

Mary Crowley Cancer Research Ctr

🇺🇸

Dallas, Texas, United States

Signal Point Clinical Research Center

🇺🇸

Middletown, Ohio, United States

Emory University - Winship Cancer Institute

🇺🇸

Atlanta, Georgia, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

Greenville Health System Cancer Institute

🇺🇸

Greenville, South Carolina, United States

Md Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Yale Cancer Center

🇺🇸

New Haven, Connecticut, United States

Baylor Scott & White Health

🇺🇸

Temple, Texas, United States

Montefiore Medical Center

🇺🇸

Bronx, New York, United States

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