Neutropenia, Breast Cancer
Conditions
Brief summary
A Phase I, dose escalation study to evaluate the safety and pharmacokinetics/pharmacodynamics of F-627 in female breast cancer patients who received up to 4 cycles of Epirubicin and Cyclophosphamide. 18 patients (6 patients each cohort) were assigned to three escalated dose cohorts of 80, 240 and 320 µg/kg.
Detailed description
A Phase I, dose escalation study to evaluate the safety and pharmacokinetics/pharmacodynamics of F-627 in female breast cancer patients receiving 4 cycles of EC (Epirubicin plus Cyclophosphamide) chemotherapy. 18 patients (6 patients each cohort) were assigned to three sequential doses cohort of F-627 at the dose of 80, 240 and 320 µg/kg. The patients received chemotherapy (100 mg/m\^2 epirubicin and 600 mg/m\^2 cyclophosphamide) administrated by i.v. injection on Day 1 and F-627 by s.c. injection on Day 3 of each cycle for 4 cycles. If no dose-limiting toxicity (DLT) was observed in 6 patients during first cycle, the next cohort was escalated. Blood samples were collected for completed blood counts with differential, serum F-627 concentration and safety evaluation at different point following F-672 injection. The decision to proceed to the next higher dose was made jointly by the sponsor's medical expert and the investigator based upon the review of safety data in the first cycle treatment.
Interventions
DRUGF-627
F-627 subcutaneous injection on Day 3 of each cycle for 4 cycles. Dose-escalation method was used.
DRUGEC regimen
Epirubicin 100 mg/m\^2 (in vein) and Cyclophosphamide 600 mg/m\^2 (in vein) on Day 1 of each cycle for 4 cycles.
Sponsors
Fudan University
EVIVE Biotechnology
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. 18-75 years old. 2. Female postoperative breast cancer patients who require adjuvant chemotherapy, and are planned to receive 4 cycles of EC chemotherapy; 3. East Cooperative Oncology Group (ECOG) performance 0-1. 4. Absolute neutrophil count (ANC) ≥ 2.0 × 10\^9/L, hemoglobin (Hb) ≥ 11.0 g/dl, and platelets (PLT) ≥ 100 × 10\^9/L prior to chemotherapy. 5. Hepatic and renal function within the normal range;. 6. Left ventricular ejection fraction (LVEF) \> 50%. 7. Willing to sign the informed consent form and able to comply with protocol requirements
Exclusion criteria
1. Women in pregnancy or breastfeeding; Women of child-bearing potential have a positive pregnancy test result prior to the first dose; 2. Life expectancy less than 12 months; 3. Radiation therapy within 4 weeks prior to enrollment; 4. Breast cancer patients who have received neoadjuvant chemotherapy before radical mastectomy; 5. Prior bone marrow or stem cell transplant; 6. With other malignant tumors other than breast cancer; 7. Have received granulocyte colony stimulating factor (G-CSF) treatment within 6 weeks prior to enrollment; 8. Diagnosed with acute congestive heart failure, cardiomyopathy, or myocardial infarction by clinical diagnosis, electrocardiograph (ECG) or other approaches; 9. With any disease that may cause splenomegaly; 10. With acute infection, chronic active Hepatitis B within 1 year (unless patients tested negative for HBsAg prior to enrollment), or Hepatitis C; 11. History of tuberculosis (TB); history of TB exposure, unless negative for tuberculin test; TB patients undergoing treatment; or suspected TB evaluated by chest x-ray; 12. Known human immunodeficiency virus (HIV) positive or acquired immune deficiency syndrome (AIDS); 13. With sickle cell anemia; 14. With alcohol or drug abuse that may affect the compliance with the study; 15. With known hypersensitivity to E. coli derived proteins, G-CSF, or excipients; 16. Has received any other investigational drug within 4 weeks prior to enrollment; 17. Patients with diseases or symptoms unsuitable for participating in the clinical trial based on the investigator's judgment;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Up to 4 cycles (about 84 days) | Safety endpoints include incidence rate and severity of adverse events (AEs), laboratory measurements, physical examinations, vital signs, and performance status. Severity of AEs were assessed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.03 criteria. |
| Tolerability (Dose-limiting Toxicity) of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Up to 21 days | Tolerability should be assessed by dose-limiting toxicity (DLT). DLT is defined as any grade 3 or greater adverse event related to the investigational drug that observed in cycle 1 (21 days). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 and cycle 3 (each cycle was about 21 days) | There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using ELISA. |
| Area Under Curve (AUC)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 and cycle 3 (each cycle was about 21 days) | There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using ELISA. |
| Vz/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 and cycle 3 (each cycle was about 21 days) | There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using ELISA. |
| Cl/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 and cycle 3 (each cycle was about 21 days) | There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using ELISA. |
| Mean Residence Time (MRT)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 and cycle 3 (each cycle was about 21 days) | There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using ELISA. |
| T1/2 of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 and cycle 3 (each cycle was about 21 days) | There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using enzyme linked immunosorbent assay (ELISA). |
| Percentage of Subjects With Grade 4 Neutropenia (< 0.5 × 10^9/L) | Up to 4 cycles (84 days) | For cycle 1, starting on day 3, oral temperature measurement and routine blood test (including ANC) will be performed daily until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle; for chemotherapy cycles 2-4 (day 3-day 21 of each chemotherapy cycle, i.e., day 24-day 84 of the study), starting on day 3, oral temperature measurement and routine blood test will be performed every other day until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle. |
| Duration of Absolute Neutrophil Count (ANC)< 0.5 × 10^9/L (Days) | Up to 4 cycles (84 days) | For cycle 1, starting on day 3, oral temperature measurement and routine blood test (including ANC) will be performed daily until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle; for chemotherapy cycles 2-4 (day 3-day 21 of each chemotherapy cycle, i.e., day 24-day 84 of the study), starting on day 3, oral temperature measurement and routine blood test will be performed every other day until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle. |
| Duration of Absolute Neutrophil Count (ANC)< 1.0 × 10^9/L (Days) | Up to 4 cycles (84 days) | For cycle 1, starting on day 3, oral temperature measurement and routine blood test (including ANC) will be performed daily until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle; for chemotherapy cycles 2-4 (day 3-day 21 of each chemotherapy cycle, i.e., day 24-day 84 of the study), starting on day 3, oral temperature measurement and routine blood test will be performed every other day until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle. |
| Absolute Neutrophil Count (ANC) Nadir (10^9 Cells/L) | Up to 4 cycles (84 days) | For cycle 1, starting on day 3, oral temperature measurement and routine blood test (including ANC) will be performed daily until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle; for chemotherapy cycles 2-4 (day 3-day 21 of each chemotherapy cycle, i.e., day 24-day 84 of the study), starting on day 3, oral temperature measurement and routine blood test will be performed every other day until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle. |
| Time (Days) of Absolute Neutrophil Count (ANC) Recovered to 1.0 × 10^9/L From Nadir | Up to 4 cycles (84 days) | For cycle 1, starting on day 3, oral temperature measurement and routine blood test (including ANC) will be performed daily until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle; for chemotherapy cycles 2-4 (day 3-day 21 of each chemotherapy cycle, i.e., day 24-day 84 of the study), starting on day 3, oral temperature measurement and routine blood test will be performed every other day until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle. |
| Percentage of Subjects With Grade 3 or 4 Neutropenia (< 1.0 × 10^9/L) | Up to 4 cycles (84 days) | For cycle 1, starting on day 3, oral temperature measurement and routine blood test (including ANC) will be performed daily until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle; for chemotherapy cycles 2-4 (day 3-day 21 of each chemotherapy cycle, i.e., day 24-day 84 of the study), starting on day 3, oral temperature measurement and routine blood test will be performed every other day until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle. |
| Cmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 and cycle 3 (each cycle was about 21 days) | There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using ELISA. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| F-627 80 µg/kg F-627 at the dose of 80 µg/kg administrated by s.c. injection on Day 3 of each cycle for 4 cycles.
F-627: F-627 subcutaneous injection on Day 3 of each cycle for 4 cycles. Dose-escalation method was used.
EC regimen: Epirubicin 100 mg/m\^2 (in vein) and Cyclophosphamide 600 mg/m\^2 (in vein) on Day 1 of each cycle for 4 cycles. | 6 |
| F-627 240 µg/kg F-627 at the dose of 240 µg/kg administrated by s.c. injection on Day 3 of each cycle for 4 cycles.
F-627: F-627 subcutaneous injection on Day 3 of each cycle for 4 cycles. Dose-escalation method was used.
EC regimen: Epirubicin 100 mg/m\^2 (in vein) and Cyclophosphamide 600 mg/m\^2 (in vein) on Day 1 of each cycle for 4 cycles. | 6 |
| F-627 320 µg/kg F-627 at the dose of 320 µg/kg administrated by s.c. injection on Day 3 of each cycle for 4 cycles.
F-627: F-627 subcutaneous injection on Day 3 of each cycle for 4 cycles. Dose-escalation method was used.
EC regimen: Epirubicin 100 mg/m\^2 (in vein) and Cyclophosphamide 600 mg/m\^2 (in vein) on Day 1 of each cycle for 4 cycles. | 6 |
| Total | 18 |
Baseline characteristics
| Characteristic | F-627 80 µg/kg | F-627 240 µg/kg | F-627 320 µg/kg | Total |
|---|---|---|---|---|
| Age, Continuous | 45.8 years STANDARD_DEVIATION 9.5 | 49.0 years STANDARD_DEVIATION 4.9 | 54.5 years STANDARD_DEVIATION 11.2 | 49.8 years STANDARD_DEVIATION 9.17 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 6 participants | 6 participants | 6 participants | 18 participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 6 | 1 / 6 | 0 / 6 |
Outcome results
Primary
Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy.
Safety endpoints include incidence rate and severity of adverse events (AEs), laboratory measurements, physical examinations, vital signs, and performance status. Severity of AEs were assessed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.03 criteria.
Time frame: Up to 4 cycles (about 84 days)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| F-627 80 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported of investigational drug-related serious adverse events (SAEs) | 0 Participants |
| F-627 80 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported AEs | 6 Participants |
| F-627 80 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported grade 3 or greater TEAEs | 6 Participants |
| F-627 80 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported serious adverse events (SAEs) | 0 Participants |
| F-627 80 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported TEAEs | 6 Participants |
| F-627 80 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported grade 3 or greater investigational drug-related TEAEs | 0 Participants |
| F-627 80 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported investigational drug-related TEAEs | 3 Participants |
| F-627 80 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported TEAEs leading to permanent discontinuation | 0 Participants |
| F-627 240 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported investigational drug-related TEAEs | 3 Participants |
| F-627 240 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported AEs | 6 Participants |
| F-627 240 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported serious adverse events (SAEs) | 1 Participants |
| F-627 240 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported of investigational drug-related serious adverse events (SAEs) | 0 Participants |
| F-627 240 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported grade 3 or greater investigational drug-related TEAEs | 0 Participants |
| F-627 240 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported TEAEs leading to permanent discontinuation | 0 Participants |
| F-627 240 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported grade 3 or greater TEAEs | 4 Participants |
| F-627 240 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported TEAEs | 6 Participants |
| F-627 320 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported of investigational drug-related serious adverse events (SAEs) | 0 Participants |
| F-627 320 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported AEs | 6 Participants |
| F-627 320 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported TEAEs | 6 Participants |
| F-627 320 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported investigational drug-related TEAEs | 4 Participants |
| F-627 320 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported grade 3 or greater TEAEs | 5 Participants |
| F-627 320 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported grade 3 or greater investigational drug-related TEAEs | 0 Participants |
| F-627 320 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported TEAEs leading to permanent discontinuation | 0 Participants |
| F-627 320 µg/kg | Evaluate the Safety of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | Number of subjects who reported serious adverse events (SAEs) | 0 Participants |
Primary
Tolerability (Dose-limiting Toxicity) of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy.
Tolerability should be assessed by dose-limiting toxicity (DLT). DLT is defined as any grade 3 or greater adverse event related to the investigational drug that observed in cycle 1 (21 days).
Time frame: Up to 21 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| F-627 80 µg/kg | Tolerability (Dose-limiting Toxicity) of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | 0 Participants |
| F-627 240 µg/kg | Tolerability (Dose-limiting Toxicity) of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | 0 Participants |
| F-627 320 µg/kg | Tolerability (Dose-limiting Toxicity) of F-627 for Injection in the Treatment of Female Postoperative Patients With Breast Cancer Who Require Adjuvant Chemotherapy. | 0 Participants |
Secondary
Absolute Neutrophil Count (ANC) Nadir (10^9 Cells/L)
For cycle 1, starting on day 3, oral temperature measurement and routine blood test (including ANC) will be performed daily until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle; for chemotherapy cycles 2-4 (day 3-day 21 of each chemotherapy cycle, i.e., day 24-day 84 of the study), starting on day 3, oral temperature measurement and routine blood test will be performed every other day until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle.
Time frame: Up to 4 cycles (84 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F-627 80 µg/kg | Absolute Neutrophil Count (ANC) Nadir (10^9 Cells/L) | ANC Nadir (10^9/L) in cycle 2 | 1.57 10^9 cells/L | Standard Deviation 0.339 |
| F-627 80 µg/kg | Absolute Neutrophil Count (ANC) Nadir (10^9 Cells/L) | ANC Nadir (10^9/L) in cycle 1 | 0.50 10^9 cells/L | Standard Deviation 0.352 |
| F-627 80 µg/kg | Absolute Neutrophil Count (ANC) Nadir (10^9 Cells/L) | ANC Nadir (10^9/L) in cycle 3 | 1.52 10^9 cells/L | Standard Deviation 0.833 |
| F-627 80 µg/kg | Absolute Neutrophil Count (ANC) Nadir (10^9 Cells/L) | ANC Nadir (10^9/L) in cycle 4 | 0.87 10^9 cells/L | Standard Deviation 0.589 |
| F-627 240 µg/kg | Absolute Neutrophil Count (ANC) Nadir (10^9 Cells/L) | ANC Nadir (10^9/L) in cycle 4 | 2.02 10^9 cells/L | Standard Deviation 1.551 |
| F-627 240 µg/kg | Absolute Neutrophil Count (ANC) Nadir (10^9 Cells/L) | ANC Nadir (10^9/L) in cycle 1 | 0.90 10^9 cells/L | Standard Deviation 1.056 |
| F-627 240 µg/kg | Absolute Neutrophil Count (ANC) Nadir (10^9 Cells/L) | ANC Nadir (10^9/L) in cycle 2 | 1.97 10^9 cells/L | Standard Deviation 1.193 |
| F-627 240 µg/kg | Absolute Neutrophil Count (ANC) Nadir (10^9 Cells/L) | ANC Nadir (10^9/L) in cycle 3 | 2.42 10^9 cells/L | Standard Deviation 2.26 |
| F-627 320 µg/kg | Absolute Neutrophil Count (ANC) Nadir (10^9 Cells/L) | ANC Nadir (10^9/L) in cycle 4 | 1.63 10^9 cells/L | Standard Deviation 0.862 |
| F-627 320 µg/kg | Absolute Neutrophil Count (ANC) Nadir (10^9 Cells/L) | ANC Nadir (10^9/L) in cycle 3 | 2.20 10^9 cells/L | Standard Deviation 0.976 |
| F-627 320 µg/kg | Absolute Neutrophil Count (ANC) Nadir (10^9 Cells/L) | ANC Nadir (10^9/L) in cycle 1 | 0.72 10^9 cells/L | Standard Deviation 0.36 |
| F-627 320 µg/kg | Absolute Neutrophil Count (ANC) Nadir (10^9 Cells/L) | ANC Nadir (10^9/L) in cycle 2 | 2.33 10^9 cells/L | Standard Deviation 0.841 |
Secondary
Area Under Curve (AUC)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3
There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using ELISA.
Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F-627 80 µg/kg | Area Under Curve (AUC)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 Area Under Curve (AUC) | 2477.75 h*ng/mL | Standard Deviation 661.64 |
| F-627 80 µg/kg | Area Under Curve (AUC)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 Area Under Curve (AUC) | 1586.35 h*ng/mL | Standard Deviation 632.57 |
| F-627 240 µg/kg | Area Under Curve (AUC)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 Area Under Curve (AUC) | 15230.79 h*ng/mL | Standard Deviation 4851.43 |
| F-627 240 µg/kg | Area Under Curve (AUC)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 Area Under Curve (AUC) | 4347.35 h*ng/mL | Standard Deviation 2135.28 |
| F-627 320 µg/kg | Area Under Curve (AUC)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 Area Under Curve (AUC) | 19858.38 h*ng/mL | Standard Deviation 7503.75 |
| F-627 320 µg/kg | Area Under Curve (AUC)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 Area Under Curve (AUC) | 6556.98 h*ng/mL | Standard Deviation 2683.3 |
Secondary
Cl/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3
There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using ELISA.
Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F-627 80 µg/kg | Cl/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 Cl/F | 31.34 mL/h/kg | Standard Deviation 7.14 |
| F-627 80 µg/kg | Cl/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 Cl/F | 45.41 mL/h/kg | Standard Deviation 16.47 |
| F-627 240 µg/kg | Cl/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 Cl/F | 17.11 mL/h/kg | Standard Deviation 6.94 |
| F-627 240 µg/kg | Cl/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 Cl/F | 62.45 mL/h/kg | Standard Deviation 35.67 |
| F-627 320 µg/kg | Cl/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 Cl/F | 18.89 mL/h/kg | Standard Deviation 9.78 |
| F-627 320 µg/kg | Cl/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 Cl/F | 56.38 mL/h/kg | Standard Deviation 26.24 |
Secondary
Cmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3
There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using ELISA.
Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F-627 80 µg/kg | Cmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 Cmax | 25.77 ng/mL | Standard Deviation 7.22 |
| F-627 80 µg/kg | Cmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 Cmax | 29.06 ng/mL | Standard Deviation 27.53 |
| F-627 240 µg/kg | Cmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 Cmax | 226.80 ng/mL | Standard Deviation 101.7 |
| F-627 240 µg/kg | Cmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 Cmax | 73.09 ng/mL | Standard Deviation 26.16 |
| F-627 320 µg/kg | Cmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 Cmax | 192.87 ng/mL | Standard Deviation 76.06 |
| F-627 320 µg/kg | Cmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 Cmax | 85.17 ng/mL | Standard Deviation 46.71 |
Secondary
Duration of Absolute Neutrophil Count (ANC)< 0.5 × 10^9/L (Days)
For cycle 1, starting on day 3, oral temperature measurement and routine blood test (including ANC) will be performed daily until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle; for chemotherapy cycles 2-4 (day 3-day 21 of each chemotherapy cycle, i.e., day 24-day 84 of the study), starting on day 3, oral temperature measurement and routine blood test will be performed every other day until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle.
Time frame: Up to 4 cycles (84 days)
Population: This outcome measure applies to all participants with a valid ANC level, regardless of whether the ANC level is less than 0.5 × 10\^9/L.~The value of 0 represents the participant experienced 0 days with ANC \< 0.5 × 10\^9/L (days).~The Number of Participants Analyzed for \*each\* Row is the same with the Overall Number of Participants Analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F-627 80 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 0.5 × 10^9/L (Days) | Duration of ANC < 0.5 × 10^9/L (days) in cycle 1 | 0.8 days | Standard Deviation 0.98 |
| F-627 80 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 0.5 × 10^9/L (Days) | Duration of ANC < 0.5 × 10^9/L (days) in cycle 2 | 0 days | Standard Deviation 0 |
| F-627 80 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 0.5 × 10^9/L (Days) | Duration of ANC < 0.5 × 10^9/L (days) in cycle 3 | 0 days | Standard Deviation 0 |
| F-627 80 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 0.5 × 10^9/L (Days) | Duration of ANC < 0.5 × 10^9/L (days) in cycle 4 | 0.3 days | Standard Deviation 0.52 |
| F-627 240 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 0.5 × 10^9/L (Days) | Duration of ANC < 0.5 × 10^9/L (days) in cycle 4 | 0.3 days | Standard Deviation 0.52 |
| F-627 240 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 0.5 × 10^9/L (Days) | Duration of ANC < 0.5 × 10^9/L (days) in cycle 1 | 1.2 days | Standard Deviation 1.33 |
| F-627 240 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 0.5 × 10^9/L (Days) | Duration of ANC < 0.5 × 10^9/L (days) in cycle 3 | 0.2 days | Standard Deviation 0.41 |
| F-627 240 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 0.5 × 10^9/L (Days) | Duration of ANC < 0.5 × 10^9/L (days) in cycle 2 | 0 days | Standard Deviation 0 |
| F-627 320 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 0.5 × 10^9/L (Days) | Duration of ANC < 0.5 × 10^9/L (days) in cycle 4 | 0 days | Standard Deviation 0 |
| F-627 320 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 0.5 × 10^9/L (Days) | Duration of ANC < 0.5 × 10^9/L (days) in cycle 2 | 0 days | Standard Deviation 0 |
| F-627 320 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 0.5 × 10^9/L (Days) | Duration of ANC < 0.5 × 10^9/L (days) in cycle 3 | 0 days | Standard Deviation 0 |
| F-627 320 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 0.5 × 10^9/L (Days) | Duration of ANC < 0.5 × 10^9/L (days) in cycle 1 | 0.5 days | Standard Deviation 0.84 |
Secondary
Duration of Absolute Neutrophil Count (ANC)< 1.0 × 10^9/L (Days)
For cycle 1, starting on day 3, oral temperature measurement and routine blood test (including ANC) will be performed daily until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle; for chemotherapy cycles 2-4 (day 3-day 21 of each chemotherapy cycle, i.e., day 24-day 84 of the study), starting on day 3, oral temperature measurement and routine blood test will be performed every other day until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle.
Time frame: Up to 4 cycles (84 days)
Population: This outcome measure applies to all participants with a valid ANC level, regardless of whether the ANC level is less than 1.0 × 10\^9/L.~The value of 0 represents the participant experienced 0 days with ANC \< 1.0 × 10\^9/L (days).~The Number of Participants Analyzed for \*each\* Row is the same with the Overall Number of Participants Analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F-627 80 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 1.0 × 10^9/L (Days) | Duration of ANC < 1.0 × 10^9/L (days) in cycle 4 | 1.0 days | Standard Deviation 1.1 |
| F-627 80 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 1.0 × 10^9/L (Days) | Duration of ANC < 1.0 × 10^9/L (days) in cycle 2 | 0 days | Standard Deviation 0 |
| F-627 80 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 1.0 × 10^9/L (Days) | Duration of ANC < 1.0 × 10^9/L (days) in cycle 3 | 0.7 days | Standard Deviation 0.82 |
| F-627 80 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 1.0 × 10^9/L (Days) | Duration of ANC < 1.0 × 10^9/L (days) in cycle 1 | 2.8 days | Standard Deviation 0.75 |
| F-627 240 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 1.0 × 10^9/L (Days) | Duration of ANC < 1.0 × 10^9/L (days) in cycle 2 | 0.3 days | Standard Deviation 0.52 |
| F-627 240 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 1.0 × 10^9/L (Days) | Duration of ANC < 1.0 × 10^9/L (days) in cycle 4 | 0.7 days | Standard Deviation 1.03 |
| F-627 240 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 1.0 × 10^9/L (Days) | Duration of ANC < 1.0 × 10^9/L (days) in cycle 1 | 1.5 days | Standard Deviation 1.76 |
| F-627 240 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 1.0 × 10^9/L (Days) | Duration of ANC < 1.0 × 10^9/L (days) in cycle 3 | 0.3 days | Standard Deviation 0.52 |
| F-627 320 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 1.0 × 10^9/L (Days) | Duration of ANC < 1.0 × 10^9/L (days) in cycle 4 | 0.5 days | Standard Deviation 0.84 |
| F-627 320 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 1.0 × 10^9/L (Days) | Duration of ANC < 1.0 × 10^9/L (days) in cycle 3 | 0.2 days | Standard Deviation 0.41 |
| F-627 320 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 1.0 × 10^9/L (Days) | Duration of ANC < 1.0 × 10^9/L (days) in cycle 1 | 1.5 days | Standard Deviation 1.05 |
| F-627 320 µg/kg | Duration of Absolute Neutrophil Count (ANC)< 1.0 × 10^9/L (Days) | Duration of ANC < 1.0 × 10^9/L (days) in cycle 2 | 0 days | Standard Deviation 0 |
Secondary
Mean Residence Time (MRT)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3
There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using ELISA.
Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F-627 80 µg/kg | Mean Residence Time (MRT)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 Mean residence time (MRT) | 86.85 hours | Standard Deviation 11.7 |
| F-627 80 µg/kg | Mean Residence Time (MRT)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 Mean residence time (MRT) | 87.08 hours | Standard Deviation 18.97 |
| F-627 240 µg/kg | Mean Residence Time (MRT)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 Mean residence time (MRT) | 61.98 hours | Standard Deviation 18.9 |
| F-627 240 µg/kg | Mean Residence Time (MRT)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 Mean residence time (MRT) | 75.61 hours | Standard Deviation 7.44 |
| F-627 320 µg/kg | Mean Residence Time (MRT)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 Mean residence time (MRT) | 88.69 hours | Standard Deviation 18.73 |
| F-627 320 µg/kg | Mean Residence Time (MRT)0-t of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 Mean residence time (MRT) | 96.29 hours | Standard Deviation 25.61 |
Secondary
Percentage of Subjects With Grade 3 or 4 Neutropenia (< 1.0 × 10^9/L)
For cycle 1, starting on day 3, oral temperature measurement and routine blood test (including ANC) will be performed daily until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle; for chemotherapy cycles 2-4 (day 3-day 21 of each chemotherapy cycle, i.e., day 24-day 84 of the study), starting on day 3, oral temperature measurement and routine blood test will be performed every other day until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle.
Time frame: Up to 4 cycles (84 days)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| F-627 80 µg/kg | Percentage of Subjects With Grade 3 or 4 Neutropenia (< 1.0 × 10^9/L) | Percentage of subjects with grade 3 or 4 neutropenia (%) in cycle 4 | 4 Participants |
| F-627 80 µg/kg | Percentage of Subjects With Grade 3 or 4 Neutropenia (< 1.0 × 10^9/L) | Percentage of subjects with grade 3 or 4 neutropenia (%) in cycle 1 | 6 Participants |
| F-627 80 µg/kg | Percentage of Subjects With Grade 3 or 4 Neutropenia (< 1.0 × 10^9/L) | Percentage of subjects with grade 3 or 4 neutropenia (%) in cycle 3 | 3 Participants |
| F-627 80 µg/kg | Percentage of Subjects With Grade 3 or 4 Neutropenia (< 1.0 × 10^9/L) | Percentage of subjects with grade 3 or 4 neutropenia (%) in cycle 2 | 0 Participants |
| F-627 240 µg/kg | Percentage of Subjects With Grade 3 or 4 Neutropenia (< 1.0 × 10^9/L) | Percentage of subjects with grade 3 or 4 neutropenia (%) in cycle 3 | 2 Participants |
| F-627 240 µg/kg | Percentage of Subjects With Grade 3 or 4 Neutropenia (< 1.0 × 10^9/L) | Percentage of subjects with grade 3 or 4 neutropenia (%) in cycle 4 | 2 Participants |
| F-627 240 µg/kg | Percentage of Subjects With Grade 3 or 4 Neutropenia (< 1.0 × 10^9/L) | Percentage of subjects with grade 3 or 4 neutropenia (%) in cycle 2 | 2 Participants |
| F-627 240 µg/kg | Percentage of Subjects With Grade 3 or 4 Neutropenia (< 1.0 × 10^9/L) | Percentage of subjects with grade 3 or 4 neutropenia (%) in cycle 1 | 3 Participants |
| F-627 320 µg/kg | Percentage of Subjects With Grade 3 or 4 Neutropenia (< 1.0 × 10^9/L) | Percentage of subjects with grade 3 or 4 neutropenia (%) in cycle 4 | 2 Participants |
| F-627 320 µg/kg | Percentage of Subjects With Grade 3 or 4 Neutropenia (< 1.0 × 10^9/L) | Percentage of subjects with grade 3 or 4 neutropenia (%) in cycle 2 | 0 Participants |
| F-627 320 µg/kg | Percentage of Subjects With Grade 3 or 4 Neutropenia (< 1.0 × 10^9/L) | Percentage of subjects with grade 3 or 4 neutropenia (%) in cycle 3 | 1 Participants |
| F-627 320 µg/kg | Percentage of Subjects With Grade 3 or 4 Neutropenia (< 1.0 × 10^9/L) | Percentage of subjects with grade 3 or 4 neutropenia (%) in cycle 1 | 5 Participants |
Secondary
Percentage of Subjects With Grade 4 Neutropenia (< 0.5 × 10^9/L)
For cycle 1, starting on day 3, oral temperature measurement and routine blood test (including ANC) will be performed daily until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle; for chemotherapy cycles 2-4 (day 3-day 21 of each chemotherapy cycle, i.e., day 24-day 84 of the study), starting on day 3, oral temperature measurement and routine blood test will be performed every other day until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle.
Time frame: Up to 4 cycles (84 days)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| F-627 80 µg/kg | Percentage of Subjects With Grade 4 Neutropenia (< 0.5 × 10^9/L) | Percentage of subjects with grade 4 neutropenia (%) in cycle 1 | 3 Participants |
| F-627 80 µg/kg | Percentage of Subjects With Grade 4 Neutropenia (< 0.5 × 10^9/L) | Percentage of subjects with grade 4 neutropenia (%) in cycle 2 | 0 Participants |
| F-627 80 µg/kg | Percentage of Subjects With Grade 4 Neutropenia (< 0.5 × 10^9/L) | Percentage of subjects with grade 4 neutropenia (%) in cycle 3 | 0 Participants |
| F-627 80 µg/kg | Percentage of Subjects With Grade 4 Neutropenia (< 0.5 × 10^9/L) | Percentage of subjects with grade 4 neutropenia (%) in cycle 4 | 2 Participants |
| F-627 240 µg/kg | Percentage of Subjects With Grade 4 Neutropenia (< 0.5 × 10^9/L) | Percentage of subjects with grade 4 neutropenia (%) in cycle 4 | 2 Participants |
| F-627 240 µg/kg | Percentage of Subjects With Grade 4 Neutropenia (< 0.5 × 10^9/L) | Percentage of subjects with grade 4 neutropenia (%) in cycle 1 | 3 Participants |
| F-627 240 µg/kg | Percentage of Subjects With Grade 4 Neutropenia (< 0.5 × 10^9/L) | Percentage of subjects with grade 4 neutropenia (%) in cycle 3 | 1 Participants |
| F-627 240 µg/kg | Percentage of Subjects With Grade 4 Neutropenia (< 0.5 × 10^9/L) | Percentage of subjects with grade 4 neutropenia (%) in cycle 2 | 0 Participants |
| F-627 320 µg/kg | Percentage of Subjects With Grade 4 Neutropenia (< 0.5 × 10^9/L) | Percentage of subjects with grade 4 neutropenia (%) in cycle 4 | 0 Participants |
| F-627 320 µg/kg | Percentage of Subjects With Grade 4 Neutropenia (< 0.5 × 10^9/L) | Percentage of subjects with grade 4 neutropenia (%) in cycle 2 | 0 Participants |
| F-627 320 µg/kg | Percentage of Subjects With Grade 4 Neutropenia (< 0.5 × 10^9/L) | Percentage of subjects with grade 4 neutropenia (%) in cycle 3 | 0 Participants |
| F-627 320 µg/kg | Percentage of Subjects With Grade 4 Neutropenia (< 0.5 × 10^9/L) | Percentage of subjects with grade 4 neutropenia (%) in cycle 1 | 2 Participants |
Secondary
T1/2 of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3
There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using enzyme linked immunosorbent assay (ELISA).
Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| F-627 80 µg/kg | T1/2 of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 T1/2 | 49.88 hours |
| F-627 80 µg/kg | T1/2 of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 T1/2 | 73.44 hours |
| F-627 240 µg/kg | T1/2 of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 T1/2 | 34.71 hours |
| F-627 240 µg/kg | T1/2 of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 T1/2 | 61.95 hours |
| F-627 320 µg/kg | T1/2 of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 T1/2 | 56.37 hours |
| F-627 320 µg/kg | T1/2 of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 T1/2 | 44.58 hours |
Secondary
Time (Days) of Absolute Neutrophil Count (ANC) Recovered to 1.0 × 10^9/L From Nadir
For cycle 1, starting on day 3, oral temperature measurement and routine blood test (including ANC) will be performed daily until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle; for chemotherapy cycles 2-4 (day 3-day 21 of each chemotherapy cycle, i.e., day 24-day 84 of the study), starting on day 3, oral temperature measurement and routine blood test will be performed every other day until ANC recovers to no less than 1.0 × 10\^9/L from nadir, and once every 3 days thereafter until the next cycle.
Time frame: Up to 4 cycles (84 days)
Population: This outcome measure applies to all participants with a valid ANC level, regardless of whether the ANC level is less than 1.0 × 10\^9/L.~The value of 0 represents the participant experienced 0 days with ANC recovered to 1.0 × 10\^9/L from nadir.~The Number of Participants Analyzed for \*each\* Row is the same with the Overall Number of Participants Analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F-627 80 µg/kg | Time (Days) of Absolute Neutrophil Count (ANC) Recovered to 1.0 × 10^9/L From Nadir | Time (days) of ANC recovered to 1.0 × 10^9/L from nadir in cycle 4 | 1.0 days | Standard Deviation 0.89 |
| F-627 80 µg/kg | Time (Days) of Absolute Neutrophil Count (ANC) Recovered to 1.0 × 10^9/L From Nadir | Time (days) of ANC recovered to 1.0 × 10^9/L from nadir in cycle 1 | 2.5 days | Standard Deviation 0.55 |
| F-627 80 µg/kg | Time (Days) of Absolute Neutrophil Count (ANC) Recovered to 1.0 × 10^9/L From Nadir | Time (days) of ANC recovered to 1.0 × 10^9/L from nadir in cycle 3 | 1.3 days | Standard Deviation 1.63 |
| F-627 80 µg/kg | Time (Days) of Absolute Neutrophil Count (ANC) Recovered to 1.0 × 10^9/L From Nadir | Time (days) of ANC recovered to 1.0 × 10^9/L from nadir in cycle 2 | 0.0 days | Standard Deviation 0 |
| F-627 240 µg/kg | Time (Days) of Absolute Neutrophil Count (ANC) Recovered to 1.0 × 10^9/L From Nadir | Time (days) of ANC recovered to 1.0 × 10^9/L from nadir in cycle 3 | 0.7 days | Standard Deviation 1.03 |
| F-627 240 µg/kg | Time (Days) of Absolute Neutrophil Count (ANC) Recovered to 1.0 × 10^9/L From Nadir | Time (days) of ANC recovered to 1.0 × 10^9/L from nadir in cycle 4 | 0.7 days | Standard Deviation 1.03 |
| F-627 240 µg/kg | Time (Days) of Absolute Neutrophil Count (ANC) Recovered to 1.0 × 10^9/L From Nadir | Time (days) of ANC recovered to 1.0 × 10^9/L from nadir in cycle 2 | 0.7 days | Standard Deviation 1.03 |
| F-627 240 µg/kg | Time (Days) of Absolute Neutrophil Count (ANC) Recovered to 1.0 × 10^9/L From Nadir | Time (days) of ANC recovered to 1.0 × 10^9/L from nadir in cycle 1 | 1.2 days | Standard Deviation 1.47 |
| F-627 320 µg/kg | Time (Days) of Absolute Neutrophil Count (ANC) Recovered to 1.0 × 10^9/L From Nadir | Time (days) of ANC recovered to 1.0 × 10^9/L from nadir in cycle 4 | 0.7 days | Standard Deviation 1.03 |
| F-627 320 µg/kg | Time (Days) of Absolute Neutrophil Count (ANC) Recovered to 1.0 × 10^9/L From Nadir | Time (days) of ANC recovered to 1.0 × 10^9/L from nadir in cycle 2 | 0.0 days | Standard Deviation 0 |
| F-627 320 µg/kg | Time (Days) of Absolute Neutrophil Count (ANC) Recovered to 1.0 × 10^9/L From Nadir | Time (days) of ANC recovered to 1.0 × 10^9/L from nadir in cycle 3 | 0.3 days | Standard Deviation 0.82 |
| F-627 320 µg/kg | Time (Days) of Absolute Neutrophil Count (ANC) Recovered to 1.0 × 10^9/L From Nadir | Time (days) of ANC recovered to 1.0 × 10^9/L from nadir in cycle 1 | 1.0 days | Standard Deviation 0.63 |
Secondary
Tmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3
There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using ELISA.
Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| F-627 80 µg/kg | Tmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 Tmax | 24 hours |
| F-627 80 µg/kg | Tmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 Tmax | 12.00 hours |
| F-627 240 µg/kg | Tmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 Tmax | 36.00 hours |
| F-627 240 µg/kg | Tmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 Tmax | 9.10 hours |
| F-627 320 µg/kg | Tmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 Tmax | 48.15 hours |
| F-627 320 µg/kg | Tmax of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 Tmax | 12.00 hours |
Secondary
Vz/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3
There are a total of 13 blood sampling time points in each cycle: pre-dose and 2, 6, 12, 24, 36, 48, 72, 96, 120, 144, 192, and 240 hr after dosing. Two additional sampling time points, 312 and 432 hr after dosing, are included for the 320 μg/kg cohort. Serum drug concentrations of F-627 at different time points will be determined using ELISA.
Time frame: Cycle 1 and cycle 3 (each cycle was about 21 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F-627 80 µg/kg | Vz/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 Vz/F | 2457.22 mL/kg | Standard Deviation 975.35 |
| F-627 80 µg/kg | Vz/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 Vz/F | 6196.75 mL/kg | Standard Deviation 3477.13 |
| F-627 240 µg/kg | Vz/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 Vz/F | 1238.80 mL/kg | Standard Deviation 1336.92 |
| F-627 240 µg/kg | Vz/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 Vz/F | 6132.23 mL/kg | Standard Deviation 2997.45 |
| F-627 320 µg/kg | Vz/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 1 Vz/F | 1597.02 mL/kg | Standard Deviation 646.1 |
| F-627 320 µg/kg | Vz/F of F-627 in Each Dose Cohort in Cycle 1 and Cycle 3 | Cycle 3 Vz/F | 4079.81 mL/kg | Standard Deviation 2189.98 |