Breast Cancer, Cholangiocarcinoma, Endometrial Cancer, Gastric Cancer, Lung Cancer, MPN, Multiple Myeloma, Myeloproliferative Neoplasms, Solid Tumor, UC, Urothelial Cancer
Conditions
Keywords
alterations in FGF or FGFR, squamous non-small cell lung cancer, gastric cancer, urothelial cancer, endometrial cancer, multiple myeloma, MPN
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).
Interventions
DRUGPemigatinib
DRUGGemcitabine
DRUGPembrolizumab
DRUGDocetaxel
DRUGTrastuzumab
DRUGRetifanlimab
DRUGCisplatin
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 TEAE | up 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 2 | predose 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 2 | predose 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 2 | predose 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 2 | predose 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
| Measure | Time frame | Description |
|---|---|---|
| Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 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 | 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: 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. |
| 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: Cmax Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States | Cycles 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: Tmax Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States | Cycles 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: t1/2 Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States | Cycles 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. |
| 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 | Cycles 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) States | Cycles 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. |
| 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: Vz/F Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States | Cycles 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. |
| Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | predose 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 1 | predose 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: AUClast of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | predose 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: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | predose 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. |
| 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: 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. |
| 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. |
| 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 | Cycles 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. |
| 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: ORR | up 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 1 | 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 | 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 1 | 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 | 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 1 | 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 | AUClast was defined as the area under the plasma or serum concentration-time curve from the time of dosing to the last measurable concentration. |
Countries
Denmark, United States
Participant flow
Recruitment details
This study was conducted at 15 study sites: 14 sites in the United States and 1 site in Denmark. The study was conducted in 3 parts. Participants self-administered once daily doses of pemigatinib on a 2-weeks-on/1-week-off therapy (intermittent) or continuous schedule in 21-day cycles. Participants also self-administered twice daily doses of pemigatinib on a continuous schedule.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD Participants 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. | 3 |
| Part 1: Intermittent Pemigatinib 6 mg QD Participants 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. | 4 |
| Part 1: Intermittent Pemigatinib 9 mg QD 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. | 3 |
| Part 1: Intermittent Pemigatinib 13.5 mg QD 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. | 6 |
| Part 1: Intermittent Pemigatinib 20 mg QD Participants 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. | 6 |
| Part 1: Continuous Pemigatinib 9 mg QD Participants self-administered oral pemigatinib 9 mg QD on Days 1 through 21 of each 21-day cycle. | 9 |
| Part 1: Continuous Pemigatinib 13.5 mg QD Participants self-administered oral pemigatinib 13.5 mg QD on Days 1 through 21 of each 21-day cycle. | 10 |
| Part 1: Continuous Pemigatinib 20 mg QD Participants self-administered oral pemigatinib 20 mg QD on Days 1 through 21 of each 21-day cycle. | 9 |
| Part 1: Continuous Pemigatinib 7.5 mg BID Participants self-administered oral pemigatinib 7.5 mg twice daily (BID) on Days 1 through 21 of each 21-day cycle. | 4 |
| Part 1: Continuous Pemigatinib 10 mg BID Participants self-administered oral pemigatinib 10 mg BID on Days 1 through 21 of each 21-day cycle. | 3 |
| Part 2: Intermittent Pemigatinib 9 mg QD 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. | 4 |
| Part 2: Intermittent Pemigatinib 13.5 mg QD 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. | 44 |
| Part 2: Continuous Pemigatinib 9 mg QD Participants self-administered oral pemigatinib 9 mg QD on Days 1 through 21 of each 21-day cycle. | 5 |
| Part 2: Continuous Pemigatinib 13.5 mg QD Participants self-administered oral pemigatinib 13.5 mg QD on Days 1 through 21 of each 21-day cycle. | 20 |
| Part 2: Continuous Pemigatinib 20 mg QD Participants self-administered oral pemigatinib 20 mg QD on Days 1 through 21 of each 21-day cycle. | 6 |
| Part 3: Gem/Cis/Intermittent Pemigatinib 9 mg Participants received gemcitabine (Gem) intravenously starting at 1000 mg/meters squared (m\^2) on Days 1 and 8 of each 21-day cycle. Cisplatin (Cis) was administered intravenously starting at 70 mg/m\^2 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. | 1 |
| Part 3: Gem/Cis/Intermittent Pemigatinib 13.5 mg Participants received gemcitabine intravenously starting at 1000 mg/m\^2 on Days 1 and 8 of each 21-day cycle. Cisplatin was administered intravenously starting at 70 mg/m\^2 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. | 7 |
| Part 3: Tras/Intermittent Pemigatinib 13.5 mg Trastuzumab (Tras) was administered as an open-label, commercial product at an initial intravenous dose of 8 mg/kilograms (kg), followed by 6 mg/kg intravenously 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. | 6 |
| Part 3: Doc/Intermittent Pemigatinib 13.5 mg Participants received docetaxel (Doc) intravenously starting at 75 mg/m\^2 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. | 7 |
| Part 3: Pem/Intermittent Pemigatinib 9 mg Participants received pembrolizumab (Pem) intravenously at 200 mg 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. | 3 |
| Part 3: Pem/Intermittent Pemigatinib 13.5 mg Participants received pembrolizumab intravenously at 200 mg 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. | 14 |
| Part 3: Pem/Continuous Pemigatinib 13.5 mg Participants received pembrolizumab intravenously at 200 mg 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. | 9 |
| Part 3: Ref/Continuous Pemigatinib 9 mg Retifanlimab (Ref) was administered once every 4 weeks on a 28-day cycle as an open-label product, at an initial intravenous dose of 500 mg. Participants self-administered oral pemigatinib 9 mg QD on Days 1 through 21 of each 21-day cycle. | 7 |
| Part 3: Ref/Continuous Pemigatinib 13.5 mg Retifanlimab was administered once every 4 weeks on a 28-day cycle as an open-label product, at an initial intravenous dose of 500 mg. Participants self-administered oral pemigatinib 13.5 mg QD on Days 1 through 21 of each 21-day cycle. | 9 |
| Part 3: Ref/Continuous Pemigatinib 20 mg Retifanlimab was administered once every 4 weeks on a 28-day cycle as an open-label product, at an initial intravenous dose of 500 mg. Participants self-administered oral pemigatinib 20 mg QD on Days 1 through 21 of each 21-day cycle. | 2 |
| Total | 201 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 | FG021 | FG022 | FG023 | FG024 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Monotherapy Dose Escalation | Clinical Decline; Withdrew by Physician | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Monotherapy Dose Escalation | Death | 2 | 2 | 3 | 6 | 6 | 6 | 5 | 8 | 4 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Monotherapy Dose Escalation | Disease Progression | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Monotherapy Dose Escalation | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Monotherapy Dose Escalation | Study Terminated by Sponsor | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Monotherapy Dose Escalation | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2: Monotherapy Dose Expansion | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 29 | 4 | 15 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2: Monotherapy Dose Expansion | Disease Progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2: Monotherapy Dose Expansion | Study Terminated by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2: Monotherapy Dose Expansion | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 13 | 1 | 2 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 3: Combination Therapy | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part 3: Combination Therapy | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 7 | 5 | 5 | 3 | 7 | 5 | 6 | 3 | 0 |
| Part 3: Combination Therapy | Disease Progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 0 |
| Part 3: Combination Therapy | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
| Part 3: Combination Therapy | Placed on Hospice; Declined Further Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part 3: Combination Therapy | Rolled Over to Another Protocol after Receiving Same Treatment | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Part 3: Combination Therapy | Study Terminated by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 2 | 1 |
| Part 3: Combination Therapy | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Part 1: Intermittent Pemigatinib 6 mg QD | Part 1: Intermittent Pemigatinib 9 mg QD | Part 1: Intermittent Pemigatinib 13.5 mg QD | Part 1: Intermittent Pemigatinib 20 mg QD | Part 1: Continuous Pemigatinib 9 mg QD | Part 1: Continuous Pemigatinib 13.5 mg QD | Part 1: Continuous Pemigatinib 20 mg QD | Part 1: Continuous Pemigatinib 7.5 mg BID | Part 1: Continuous Pemigatinib 10 mg BID | Part 2: Intermittent Pemigatinib 9 mg QD | Part 2: Intermittent Pemigatinib 13.5 mg QD | Part 2: Continuous Pemigatinib 9 mg QD | Part 2: Continuous Pemigatinib 13.5 mg QD | Part 2: Continuous Pemigatinib 20 mg QD | Part 3: Pem/Intermittent Pemigatinib 13.5 mg | Part 3: Gem/Cis/Intermittent Pemigatinib 9 mg | Part 3: Gem/Cis/Intermittent Pemigatinib 13.5 mg | Part 3: Tras/Intermittent Pemigatinib 13.5 mg | Part 3: Doc/Intermittent Pemigatinib 13.5 mg | Part 3: Pem/Intermittent Pemigatinib 9 mg | Part 3: Pem/Continuous Pemigatinib 13.5 mg | Part 3: Ref/Continuous Pemigatinib 9 mg | Part 3: Ref/Continuous Pemigatinib 13.5 mg | Part 3: Ref/Continuous Pemigatinib 20 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 60.7 years STANDARD_DEVIATION 11.24 | 45.5 years STANDARD_DEVIATION 17.31 | 56.3 years STANDARD_DEVIATION 4.93 | 59.0 years STANDARD_DEVIATION 14.79 | 56.2 years STANDARD_DEVIATION 11.89 | 57.9 years STANDARD_DEVIATION 15.7 | 61.2 years STANDARD_DEVIATION 16.88 | 56.3 years STANDARD_DEVIATION 15.19 | 66.8 years STANDARD_DEVIATION 4.57 | 68.7 years STANDARD_DEVIATION 15.89 | 50.3 years STANDARD_DEVIATION 12.39 | 57.7 years STANDARD_DEVIATION 11.81 | 63.8 years STANDARD_DEVIATION 10.69 | 57.4 years STANDARD_DEVIATION 13.78 | 58.3 years STANDARD_DEVIATION 8.8 | 64.7 years STANDARD_DEVIATION 10.5 | 61.0 years | 54.1 years STANDARD_DEVIATION 10.43 | 47.8 years STANDARD_DEVIATION 14.44 | 62.4 years STANDARD_DEVIATION 9.16 | 55.0 years STANDARD_DEVIATION 15.72 | 61.8 years STANDARD_DEVIATION 10.89 | 63.4 years STANDARD_DEVIATION 11.43 | 66.9 years STANDARD_DEVIATION 8.8 | 68.0 years STANDARD_DEVIATION 7.07 | 59.0 years STANDARD_DEVIATION 12.61 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 4 Participants | 0 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 3 Participants | 3 Participants | 6 Participants | 4 Participants | 8 Participants | 9 Participants | 9 Participants | 4 Participants | 3 Participants | 3 Participants | 39 Participants | 5 Participants | 16 Participants | 6 Participants | 13 Participants | 1 Participants | 7 Participants | 6 Participants | 7 Participants | 3 Participants | 8 Participants | 7 Participants | 9 Participants | 1 Participants | 182 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized American-Indian/Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Black/African-American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 7 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 15 Participants |
| Race/Ethnicity, Customized Captured as Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White/Caucasian | 3 Participants | 4 Participants | 2 Participants | 6 Participants | 5 Participants | 8 Participants | 10 Participants | 8 Participants | 4 Participants | 3 Participants | 3 Participants | 37 Participants | 5 Participants | 18 Participants | 6 Participants | 10 Participants | 1 Participants | 5 Participants | 6 Participants | 6 Participants | 2 Participants | 9 Participants | 7 Participants | 9 Participants | 1 Participants | 178 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 6 Participants | 5 Participants | 6 Participants | 0 Participants | 2 Participants | 3 Participants | 27 Participants | 5 Participants | 10 Participants | 5 Participants | 5 Participants | 0 Participants | 3 Participants | 4 Participants | 3 Participants | 1 Participants | 3 Participants | 7 Participants | 5 Participants | 1 Participants | 113 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 5 Participants | 3 Participants | 4 Participants | 1 Participants | 1 Participants | 17 Participants | 0 Participants | 10 Participants | 1 Participants | 9 Participants | 1 Participants | 4 Participants | 2 Participants | 4 Participants | 2 Participants | 6 Participants | 0 Participants | 4 Participants | 1 Participants | 88 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 2 / 4 | 6 / 7 | 37 / 50 | 6 / 6 | 10 / 14 | 21 / 30 | 10 / 15 | 4 / 4 | 2 / 3 | 1 / 1 | 7 / 7 | 5 / 6 | 5 / 7 | 3 / 3 | 9 / 14 | 6 / 9 | 6 / 7 | 3 / 9 | 0 / 2 |
| other Total, other adverse events | 3 / 3 | 3 / 4 | 7 / 7 | 50 / 50 | 6 / 6 | 14 / 14 | 30 / 30 | 15 / 15 | 4 / 4 | 3 / 3 | 1 / 1 | 7 / 7 | 6 / 6 | 7 / 7 | 3 / 3 | 14 / 14 | 9 / 9 | 7 / 7 | 9 / 9 | 2 / 2 |
| serious Total, serious adverse events | 1 / 3 | 0 / 4 | 3 / 7 | 21 / 50 | 3 / 6 | 6 / 14 | 14 / 30 | 7 / 15 | 2 / 4 | 2 / 3 | 1 / 1 | 3 / 7 | 0 / 6 | 6 / 7 | 1 / 3 | 7 / 14 | 3 / 9 | 4 / 7 | 5 / 9 | 2 / 2 |
Outcome results
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.
Time frame: predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles
Population: Pharmacokinetic/Pharmacodynamic (PK/PD) Population: all enrolled participants who had PK/PD data. The average serum concentration of phosphate on Cycle 1 Days 8 and 15 was chosen as a dependent variable for E-R analysis, which was independent of the intermittent dosing and continuous dosing regimens. Therefore, the intermittent dosing and continuous dosing groups from Parts 1 and 2 were combined into a single analysis group for E-R analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | E0 Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2 | 3.66 milligrams per deciliter (mg/dL) | Geometric Coefficient of Variation 1.91 |
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.
Time frame: predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles
Population: PK/PD Population. The average serum concentration of phosphate on Cycle 1 Days 8 and 15 was chosen as a dependent variable for E-R analysis, which was independent of the intermittent dosing and continuous dosing regimens. Therefore, the intermittent dosing and continuous dosing groups from Parts 1 and 2 were combined into a single analysis group for E-R analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | EC50 Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2 | 1573 hours*nanomoles | Geometric Coefficient of Variation 21.6 |
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.
Time frame: predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles
Population: PK/PD Population. The average serum concentration of phosphate on Cycle 1 Days 8 and 15 was chosen as a dependent variable for E-R analysis, which was independent of the intermittent dosing and continuous dosing regimens. Therefore, the intermittent dosing and continuous dosing groups from Parts 1 and 2 were combined into a single analysis group for E-R analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Emax Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2 | 5.76 mg/dL | Geometric Coefficient of Variation 7.76 |
Primary
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
Population: PK/PD Population. The average serum concentration of phosphate on Cycle 1 Days 8 and 15 was chosen as a dependent variable for E-R analysis, which was independent of the intermittent dosing and continuous dosing regimens. Therefore, the intermittent dosing and continuous dosing groups from Parts 1 and 2 were combined into a single analysis group for E-R analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Highest Serum Phosphate Concentration Following Pemigatinib as Monotherapy in Parts 1 and 2 | Minimum value in range of highest values for all participants | 3.5 mg/dL |
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Highest Serum Phosphate Concentration Following Pemigatinib as Monotherapy in Parts 1 and 2 | Maximum value in range of highest values for all participants | 11.2 mg/dL |
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.
Time frame: up to 869 days
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Part 3: Number of Participants With Any TEAE | 1 Participants |
| Part 1: Intermittent Pemigatinib 6 mg QD | Part 3: Number of Participants With Any TEAE | 7 Participants |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Part 3: Number of Participants With Any TEAE | 6 Participants |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Part 3: Number of Participants With Any TEAE | 7 Participants |
| Part 1: Intermittent Pemigatinib 20 mg QD | Part 3: Number of Participants With Any TEAE | 3 Participants |
| Parts 1 and 2: Continuous Pemigatinib 9 mg QD | Part 3: Number of Participants With Any TEAE | 14 Participants |
| Parts 1 and 2: Continuous Pemigatinib 13.5 mg QD | Part 3: Number of Participants With Any TEAE | 9 Participants |
| Parts 1 and 2: Continuous Pemigatinib 20 mg QD | Part 3: Number of Participants With Any TEAE | 7 Participants |
| Part 1: Continuous Pemigatinib 7.5 mg BID | Part 3: Number of Participants With Any TEAE | 9 Participants |
| Part 1: Continuous Pemigatinib 10 mg BID | Part 3: Number of Participants With Any TEAE | 2 Participants |
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.
Time frame: up to 763 days
Population: Safety Population: all enrolled participants who received at least 1 dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Parts 1 and 2 Combined: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 3 Participants |
| Part 1: Intermittent Pemigatinib 6 mg QD | Parts 1 and 2 Combined: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 3 Participants |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Parts 1 and 2 Combined: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 7 Participants |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Parts 1 and 2 Combined: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 50 Participants |
| Part 1: Intermittent Pemigatinib 20 mg QD | Parts 1 and 2 Combined: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 6 Participants |
| Parts 1 and 2: Continuous Pemigatinib 9 mg QD | Parts 1 and 2 Combined: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 14 Participants |
| Parts 1 and 2: Continuous Pemigatinib 13.5 mg QD | Parts 1 and 2 Combined: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 30 Participants |
| Parts 1 and 2: Continuous Pemigatinib 20 mg QD | Parts 1 and 2 Combined: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 15 Participants |
| Part 1: Continuous Pemigatinib 7.5 mg BID | Parts 1 and 2 Combined: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 4 Participants |
| Part 1: Continuous Pemigatinib 10 mg BID | Parts 1 and 2 Combined: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 3 Participants |
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.
Time frame: up to 126 days
Population: Efficacy Evaluable Population: all enrolled participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Part 2: Overall Response Rate (ORR) | 25.0 percentage of participants |
| Part 1: Intermittent Pemigatinib 6 mg QD | Part 2: Overall Response Rate (ORR) | 4.5 percentage of participants |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Part 2: Overall Response Rate (ORR) | 0.0 percentage of participants |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Part 2: Overall Response Rate (ORR) | 30.0 percentage of participants |
| Part 1: Intermittent Pemigatinib 20 mg QD | Part 2: Overall Response Rate (ORR) | 0.0 percentage of participants |
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.
Time frame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Part 3: Accumulation Ratio of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 1.65 ratio | Standard Deviation 0.501 |
| Part 1: Intermittent Pemigatinib 6 mg QD | Part 3: Accumulation Ratio of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 1.53 ratio | Standard Deviation 0.381 |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Part 3: Accumulation Ratio of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 0.604 ratio | Standard Deviation 0.265 |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Part 3: Accumulation Ratio of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 1.52 ratio | Standard Deviation 0.772 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Part 3: Accumulation Ratio of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 1.90 ratio | Standard Deviation 0.432 |
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.
Time frame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 1550 hr*ng/mL | Standard Deviation 552 |
| Part 1: Intermittent Pemigatinib 6 mg QD | Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 1910 hr*ng/mL | Standard Deviation 838 |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 2920 hr*ng/mL | Standard Deviation 1070 |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 1890 hr*ng/mL | Standard Deviation 471 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 1890 hr*ng/mL | Standard Deviation 269 |
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.
Time frame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 2400 hr*ng/mL | Standard Deviation 628 |
| Part 1: Intermittent Pemigatinib 6 mg QD | Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 2400 hr*ng/mL | Standard Deviation 967 |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 1650 hr*ng/mL | Standard Deviation 1060 |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 2910 hr*ng/mL | Standard Deviation 1390 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 3440 hr*ng/mL | Standard Deviation 672 |
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.
Time frame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Part 3: AUClast of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 1480 hr*ng/mL | Standard Deviation 587 |
| Part 1: Intermittent Pemigatinib 6 mg QD | Part 3: AUClast of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 1880 hr*ng/mL | Standard Deviation 821 |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Part 3: AUClast of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 2890 hr*ng/mL | Standard Deviation 1010 |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Part 3: AUClast of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 1890 hr*ng/mL | Standard Deviation 491 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Part 3: AUClast of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 2040 hr*ng/mL | Standard Deviation 513 |
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.
Time frame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Part 3: CL/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 8.03 L/hr | Standard Deviation 1.89 |
| Part 1: Intermittent Pemigatinib 6 mg QD | Part 3: CL/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 13.4 L/hr | Standard Deviation 5.46 |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Part 3: CL/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 24.5 L/hr | Standard Deviation 17.7 |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Part 3: CL/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 12.7 L/hr | Standard Deviation 9.03 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Part 3: CL/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 8.26 L/hr | Standard Deviation 1.39 |
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.
Time frame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 137 ng/mL | Standard Deviation 65.7 |
| Part 1: Intermittent Pemigatinib 6 mg QD | Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 199 ng/mL | Standard Deviation 99.6 |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 234 ng/mL | Standard Deviation 84.1 |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 214 ng/mL | Standard Deviation 98.2 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 259 ng/mL | Standard Deviation 55.4 |
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.
Time frame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 166 ng/mL | Standard Deviation 52.1 |
| Part 1: Intermittent Pemigatinib 6 mg QD | Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 255 ng/mL | Standard Deviation 119 |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 214 ng/mL | Standard Deviation 203 |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 231 ng/mL | Standard Deviation 99.4 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 404 ng/mL | Standard Deviation 41.7 |
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.
Time frame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Part 3: Cmin of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 58.0 ng/mL | Standard Deviation 31.6 |
| Part 1: Intermittent Pemigatinib 6 mg QD | Part 3: Cmin of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 56.6 ng/mL | Standard Deviation 31.3 |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Part 3: Cmin of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 48.5 ng/mL | Standard Deviation 57.8 |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Part 3: Cmin of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 63.1 ng/mL | Standard Deviation 32.4 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Part 3: Cmin of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 64.2 ng/mL | Standard Deviation 25.8 |
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.
Time frame: up to 203 days
Population: Efficacy Evaluable Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Part 3: ORR | 0.0 percentage of participants |
| Part 1: Intermittent Pemigatinib 6 mg QD | Part 3: ORR | 42.9 percentage of participants |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Part 3: ORR | 0.0 percentage of participants |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Part 3: ORR | 14.3 percentage of participants |
| Part 1: Intermittent Pemigatinib 20 mg QD | Part 3: ORR | 0.0 percentage of participants |
| Parts 1 and 2: Continuous Pemigatinib 9 mg QD | Part 3: ORR | 28.6 percentage of participants |
| Parts 1 and 2: Continuous Pemigatinib 13.5 mg QD | Part 3: ORR | 33.3 percentage of participants |
| Parts 1 and 2: Continuous Pemigatinib 20 mg QD | Part 3: ORR | 0.0 percentage of participants |
| Part 1: Continuous Pemigatinib 7.5 mg BID | Part 3: ORR | 22.2 percentage of participants |
| Part 1: Continuous Pemigatinib 10 mg BID | Part 3: ORR | 0.0 percentage of participants |
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.
Time frame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Part 3: t1/2 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 15.3 hr | Standard Deviation 0.207 |
| Part 1: Intermittent Pemigatinib 6 mg QD | Part 3: t1/2 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 17.0 hr | Standard Deviation 6.9 |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Part 3: t1/2 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 10.6 hr | Standard Deviation 3.29 |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Part 3: t1/2 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 14.7 hr | Standard Deviation 6.43 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Part 3: t1/2 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 15.3 hr | Standard Deviation 2.64 |
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.
Time frame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 1.98 hr |
| Part 1: Intermittent Pemigatinib 6 mg QD | Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 1.05 hr |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 2.00 hr |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 1.00 hr |
| Part 1: Intermittent Pemigatinib 20 mg QD | Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 | 0.783 hr |
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.
Time frame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 5.78 hr |
| Part 1: Intermittent Pemigatinib 6 mg QD | Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 1.08 hr |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 1.50 hr |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 1.90 hr |
| Part 1: Intermittent Pemigatinib 20 mg QD | Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 0.583 hr |
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.
Time frame: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Part 3: Vz/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 177 Liters | Standard Deviation 39.8 |
| Part 1: Intermittent Pemigatinib 6 mg QD | Part 3: Vz/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 303 Liters | Standard Deviation 136 |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Part 3: Vz/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 376 Liters | Standard Deviation 261 |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Part 3: Vz/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 227 Liters | Standard Deviation 82.2 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Part 3: Vz/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) | 182 Liters | Standard Deviation 43.2 |
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.
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
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Parts 1 and 2: Accumulation Ratio After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 1.09 ratio | — |
| Part 1: Intermittent Pemigatinib 6 mg QD | Parts 1 and 2: Accumulation Ratio After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 1.64 ratio | — |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Parts 1 and 2: Accumulation Ratio After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 1.36 ratio | — |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Parts 1 and 2: Accumulation Ratio After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 1.67 ratio | Standard Deviation 0.264 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Parts 1 and 2: Accumulation Ratio After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 1.71 ratio | Standard Deviation 0.534 |
| Parts 1 and 2: Continuous Pemigatinib 9 mg QD | Parts 1 and 2: Accumulation Ratio After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 1.69 ratio | Standard Deviation 0.538 |
| Parts 1 and 2: Continuous Pemigatinib 13.5 mg QD | Parts 1 and 2: Accumulation Ratio After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 1.76 ratio | Standard Deviation 0.476 |
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.
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
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 191 hr*ng/mL | — |
| Part 1: Intermittent Pemigatinib 6 mg QD | Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | NA hr*ng/mL | — |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 1010 hr*ng/mL | — |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 644 hr*ng/mL | Standard Deviation 115 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 1150 hr*ng/mL | Standard Deviation 497 |
| Parts 1 and 2: Continuous Pemigatinib 9 mg QD | Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 1840 hr*ng/mL | Standard Deviation 1080 |
| Parts 1 and 2: Continuous Pemigatinib 13.5 mg QD | Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 2850 hr*ng/mL | Standard Deviation 1050 |
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.
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
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 208 hr*ng/mL | — |
| Part 1: Intermittent Pemigatinib 6 mg QD | Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 322 hr*ng/mL | — |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 1380 hr*ng/mL | — |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 1080 hr*ng/mL | Standard Deviation 301 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 2180 hr*ng/mL | Standard Deviation 1630 |
| Parts 1 and 2: Continuous Pemigatinib 9 mg QD | Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 3010 hr*ng/mL | Standard Deviation 1890 |
| Parts 1 and 2: Continuous Pemigatinib 13.5 mg QD | Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 4350 hr*ng/mL | Standard Deviation 1480 |
p-value: 0.8577ANOVA
p-value: 0.7238ANOVA
p-value: 0.5923ANOVA
p-value: 0.7634ANOVA
p-value: 0.5749ANOVA
p-value: 0.6877ANOVA
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.
Time frame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Population: PK/PD Population. Only participants who participated in the food-effect study in Part 2 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | 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 | 2580 hr*ng/mL | Standard Deviation 999 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 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 | 2910 hr*ng/mL | Standard Deviation 1310 |
p-value: 0.305ANOVA
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.
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
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Parts 1 and 2: AUClast After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 190 hr*ng/mL | — |
| Part 1: Intermittent Pemigatinib 6 mg QD | Parts 1 and 2: AUClast After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 68.8 hr*ng/mL | — |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Parts 1 and 2: AUClast After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 1010 hr*ng/mL | — |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Parts 1 and 2: AUClast After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 641 hr*ng/mL | Standard Deviation 116 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Parts 1 and 2: AUClast After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 1140 hr*ng/mL | Standard Deviation 498 |
| Parts 1 and 2: Continuous Pemigatinib 9 mg QD | Parts 1 and 2: AUClast After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 1820 hr*ng/mL | Standard Deviation 1210 |
| Parts 1 and 2: Continuous Pemigatinib 13.5 mg QD | Parts 1 and 2: AUClast After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 2510 hr*ng/mL | Standard Deviation 935 |
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.
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
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Parts 1 and 2: CL/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 9.86 Liters per hr (L/hr) | — |
| Part 1: Intermittent Pemigatinib 6 mg QD | Parts 1 and 2: CL/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 12.8 Liters per hr (L/hr) | — |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Parts 1 and 2: CL/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 5.93 Liters per hr (L/hr) | — |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Parts 1 and 2: CL/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 12.0 Liters per hr (L/hr) | Standard Deviation 3.14 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Parts 1 and 2: CL/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 15.7 Liters per hr (L/hr) | Standard Deviation 17.7 |
| Parts 1 and 2: Continuous Pemigatinib 9 mg QD | Parts 1 and 2: CL/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 11.9 Liters per hr (L/hr) | Standard Deviation 5.72 |
| Parts 1 and 2: Continuous Pemigatinib 13.5 mg QD | Parts 1 and 2: CL/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 10.3 Liters per hr (L/hr) | Standard Deviation 3.01 |
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.
Time frame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Population: PK/PD Population. Only participants who participated in the food-effect study in Part 2 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | 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 | 12.4 L/hr | Standard Deviation 4.94 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 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 | 11.3 L/hr | Standard Deviation 4.87 |
p-value: 0.305ANOVA
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.
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
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 25.3 nanograms per milliliter (ng/mL) | — |
| Part 1: Intermittent Pemigatinib 6 mg QD | Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 13.6 nanograms per milliliter (ng/mL) | — |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 109 nanograms per milliliter (ng/mL) | — |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 64.6 nanograms per milliliter (ng/mL) | Standard Deviation 9.16 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 139 nanograms per milliliter (ng/mL) | Standard Deviation 79.8 |
| Parts 1 and 2: Continuous Pemigatinib 9 mg QD | Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 196 nanograms per milliliter (ng/mL) | Standard Deviation 121 |
| Parts 1 and 2: Continuous Pemigatinib 13.5 mg QD | Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 300 nanograms per milliliter (ng/mL) | Standard Deviation 135 |
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.
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
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 26.2 ng/mL | — |
| Part 1: Intermittent Pemigatinib 6 mg QD | Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 22.9 ng/mL | — |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 103 ng/mL | — |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 86.1 ng/mL | Standard Deviation 38 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 196 ng/mL | Standard Deviation 123 |
| Parts 1 and 2: Continuous Pemigatinib 9 mg QD | Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 271 ng/mL | Standard Deviation 151 |
| Parts 1 and 2: Continuous Pemigatinib 13.5 mg QD | Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 449 ng/mL | Standard Deviation 172 |
p-value: 0.2841ANOVA
p-value: 0.3042ANOVA
p-value: 0.1259ANOVA
p-value: 0.8214ANOVA
p-value: 0.4315ANOVA
p-value: 0.2595ANOVA
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.
Time frame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Population: PK/PD Population. Only participants who participated in the food-effect study in Part 2 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | 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 | 215 ng/mL | Standard Deviation 86.5 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 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 | 179 ng/mL | Standard Deviation 82.8 |
p-value: 0.143ANOVA
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.
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
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Parts 1 and 2: Cmin After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 3.24 ng/mL | — |
| Part 1: Intermittent Pemigatinib 6 mg QD | Parts 1 and 2: Cmin After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 7.87 ng/mL | — |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Parts 1 and 2: Cmin After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 23.9 ng/mL | — |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Parts 1 and 2: Cmin After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 30.0 ng/mL | Standard Deviation 15.1 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Parts 1 and 2: Cmin After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 49.9 ng/mL | Standard Deviation 49.6 |
| Parts 1 and 2: Continuous Pemigatinib 9 mg QD | Parts 1 and 2: Cmin After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 71.7 ng/mL | Standard Deviation 56.7 |
| Parts 1 and 2: Continuous Pemigatinib 13.5 mg QD | Parts 1 and 2: Cmin After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 104 ng/mL | Standard Deviation 93.3 |
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.
Time frame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Population: PK/PD Population. Only participants who participated in the food-effect study in Part 2 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | 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 | 61.1 ng/mL | Standard Deviation 33.5 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 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 | 65.7 ng/mL | Standard Deviation 34.7 |
p-value: 0.128ANOVA
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.
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
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Parts 1 and 2: t1/2 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 10.9 hr | — |
| Part 1: Intermittent Pemigatinib 6 mg QD | Parts 1 and 2: t1/2 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 18.1 hr | — |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Parts 1 and 2: t1/2 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 30.4 hr | — |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Parts 1 and 2: t1/2 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 21.0 hr | Standard Deviation 22.8 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Parts 1 and 2: t1/2 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 17.2 hr | Standard Deviation 9.7 |
| Parts 1 and 2: Continuous Pemigatinib 9 mg QD | Parts 1 and 2: t1/2 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 17.4 hr | Standard Deviation 9.64 |
| Parts 1 and 2: Continuous Pemigatinib 13.5 mg QD | Parts 1 and 2: t1/2 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 13.1 hr | Standard Deviation 6.01 |
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.
Time frame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Population: PK/PD Population. Only participants who participated in the food-effect study in Part 2 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | 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 | 19.2 hr | Standard Deviation 10.5 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 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 | 23.8 hr | Standard Deviation 17.5 |
p-value: 0.319ANOVA
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.
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
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 1 hours (hr) |
| Part 1: Intermittent Pemigatinib 6 mg QD | Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 5.92 hours (hr) |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 2.02 hours (hr) |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 1.14 hours (hr) |
| Part 1: Intermittent Pemigatinib 20 mg QD | Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 1.17 hours (hr) |
| Parts 1 and 2: Continuous Pemigatinib 9 mg QD | Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 1.20 hours (hr) |
| Parts 1 and 2: Continuous Pemigatinib 13.5 mg QD | Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 | 1.98 hours (hr) |
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.
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
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 1.07 hr |
| Part 1: Intermittent Pemigatinib 6 mg QD | Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 3.98 hr |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 2.02 hr |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 1.58 hr |
| Part 1: Intermittent Pemigatinib 20 mg QD | Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 1.00 hr |
| Parts 1 and 2: Continuous Pemigatinib 9 mg QD | Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 1.13 hr |
| Parts 1 and 2: Continuous Pemigatinib 13.5 mg QD | Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 1.12 hr |
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.
Time frame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Population: PK/PD Population. Only participants who participated in the food-effect study in Part 2 were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | 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 | 1.58 hr |
| Part 1: Intermittent Pemigatinib 6 mg QD | 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 | 4.02 hr |
p-value: 0.0013ANOVA
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.
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
Population: PK/PD Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | Parts 1 and 2: Vz/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 156 Liters | — |
| Part 1: Intermittent Pemigatinib 6 mg QD | Parts 1 and 2: Vz/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 334 Liters | — |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | Parts 1 and 2: Vz/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 260 Liters | — |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | Parts 1 and 2: Vz/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 301 Liters | Standard Deviation 241 |
| Part 1: Intermittent Pemigatinib 20 mg QD | Parts 1 and 2: Vz/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 246 Liters | Standard Deviation 76.1 |
| Parts 1 and 2: Continuous Pemigatinib 9 mg QD | Parts 1 and 2: Vz/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 274 Liters | Standard Deviation 165 |
| Parts 1 and 2: Continuous Pemigatinib 13.5 mg QD | Parts 1 and 2: Vz/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) | 180 Liters | Standard Deviation 49.1 |
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.
Time frame: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
Population: PK/PD Population. Only participants who participated in the food-effect study in Part 2 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | 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 | 307 Liters | Standard Deviation 139 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 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 | 364 Liters | Standard Deviation 262 |
p-value: 0.772ANOVA