Advanced Solid Tumors, Recurrent Solid Tumors
Conditions
Brief summary
The objective of the study is to investigate the pharmacokinetics of ONO-4538 administered to Korean patients with advanced or recurrent solid tumors who are refractory or intolerant to standard therapy or for whom no appropriate treatment is available.
Interventions
DRUGONO-4538
Sponsors
Ono Pharmaceutical Co. Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Increase the dose sequentially.
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female ≥ 20 years of age * Histologically or cytologically confirmed solid tumor * Patients with advanced or recurrent solid tumors who are refractory or intolerant to standard therapy or for whom no appropriate treatment is available * ECOG Performance Status is 0 to 1
Exclusion criteria
* Current or prior severe hypersensitivity to another antibody product * Multiple primary cancers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK Outcome: Tmax of ONO-4538 | 3 weeks: from the start of administration to the end of treatment phase. Actual blood sampling points are pre-dose, 1hr, 3hr, 9hr, 25hr, 49hr, 73hr, 169hr, 337hr, and 504hr. | Tmax was the time to reach the Cmax. |
| AUCinf | 3 weeks: from the start of administration to the end of treatment phase. Actual blood sampling points are pre-dose, 1hr, 3hr, 9hr, 25hr, 49hr, 73hr, 169hr, 337hr, and 504hr. | AUCinf was the area under serum concentration-time curve of ONO-4538 extrapolated to infinity. |
| T1/2 | 3 weeks: from the start of administration to the end of treatment phase. Actual blood sampling points are pre-dose, 1hr, 3hr, 9hr, 25hr, 49hr, 73hr, 169hr, 337hr, and 504hr. | T1/2 was the elimination half-life of serum concentration of ONO-4538. |
| PK Outcome: Cmax of ONO-4538 | 3 weeks: from the start of administration to the end of treatment phase. Actual blood sampling points are pre-dose, 1hr, 3hr, 9hr, 25hr, 49hr, 73hr, 169hr, 337hr, and 504hr. | Cmax was the maximum serum concentration of ONO-4538 after the single administration. |
| AUC21day | 3 weeks: from the start of administration to the end of treatment phase. Actual blood sampling points are pre-dose, 1hr, 3hr, 9hr, 25hr, 49hr, 73hr, 169hr, 337hr, and 504hr. | AUC21day was the area under serum concentration-time curve of ONO-4538 from day 0 to day 21 (last measurement). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety Outcome: The Number of Deaths | 3 weeks: from the start of administration to the end of treatment phase. | Number of subjects with TEAEs leading to death. |
| Safety Outcome: The Number of Subjects With Overall Adverse Events | 3 weeks: from the start of administration to the end of treatment phase. | Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of investigational product that first appeared following exposure to investigational product or any event already present that worsened relative to the pre-treatment state following exposure to investigational product. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ONO-4538 1 mg/kg Refer to Participant Flow . | 6 |
| ONO-4538 3 mg/kg Refer to Participant Flow . | 6 |
| ONO-4538 10 mg/kg Refer to Participant Flow . | 6 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Disease progression | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | ONO-4538 3 mg/kg | Total | ONO-4538 10 mg/kg | ONO-4538 1 mg/kg |
|---|---|---|---|---|
| Age, Continuous | 63.0 years | 56.0 years | 52.5 years | 44.5 years |
| Age, Customized >=65-<75 years | 3 Participants | 6 Participants | 1 Participants | 2 Participants |
| Age, Customized <65 years | 3 Participants | 11 Participants | 4 Participants | 4 Participants |
| Age, Customized >=75 years | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| BMI | 23.26 Kilogram per square meter | 22.57 Kilogram per square meter | 21.55 Kilogram per square meter | 22.62 Kilogram per square meter |
| Height | 161.90 Centimeter | 160.85 Centimeter | 161.35 Centimeter | 156.60 Centimeter |
| History of chemotherapy 1 regimen | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| History of chemotherapy 2 regimens | 1 Participants | 5 Participants | 2 Participants | 2 Participants |
| History of chemotherapy 3 regimens | 2 Participants | 4 Participants | 1 Participants | 1 Participants |
| History of chemotherapy 4 regimens | 1 Participants | 3 Participants | 2 Participants | 0 Participants |
| History of chemotherapy 5 regimens | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| History of chemotherapy 6 regimens | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| History of chemotherapy None | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| History of radiotherapy No | 2 Participants | 6 Participants | 2 Participants | 2 Participants |
| History of radiotherapy Yes | 4 Participants | 12 Participants | 4 Participants | 4 Participants |
| History of surgery No | 1 Participants | 4 Participants | 3 Participants | 0 Participants |
| History of surgery Yes | 5 Participants | 14 Participants | 3 Participants | 6 Participants |
| Performance status (Eastern Cooperative Oncology Group) PS 0 | 1 Participants | 8 Participants | 3 Participants | 4 Participants |
| Performance status (Eastern Cooperative Oncology Group) PS 1 | 5 Participants | 10 Participants | 3 Participants | 2 Participants |
| Region of Enrollment South Korea | 6 participants | 18 participants | 6 participants | 6 participants |
| Sex: Female, Male Female | 1 Participants | 10 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 5 Participants | 8 Participants | 2 Participants | 1 Participants |
| Type of primary cancer Colon cancer | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Type of primary cancer Gastric cancer | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Type of primary cancer Lung cancer | 1 Participants | 4 Participants | 3 Participants | 0 Participants |
| Type of primary cancer Melanoma | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Type of primary cancer Nasal cavity cancer | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Type of primary cancer Nasopharyngeal carcinoma | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Type of primary cancer Pancreatic cancer | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Type of primary cancer Rectal cancer | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Type of primary cancer Renal cell carcinoma | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Type of primary cancer Salivary gland cancer | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Type of primary cancer Sarcoma | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Weight | 63.40 Kilogram | 59.25 Kilogram | 57.50 Kilogram | 56.75 Kilogram |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 6 | 0 / 6 | 1 / 6 |
| other Total, other adverse events | 5 / 6 | 4 / 6 | 5 / 6 |
| serious Total, serious adverse events | 1 / 6 | 0 / 6 | 1 / 6 |
Outcome results
Primary
AUC21day
AUC21day was the area under serum concentration-time curve of ONO-4538 from day 0 to day 21 (last measurement).
Time frame: 3 weeks: from the start of administration to the end of treatment phase. Actual blood sampling points are pre-dose, 1hr, 3hr, 9hr, 25hr, 49hr, 73hr, 169hr, 337hr, and 504hr.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ONO-4538 1 mg/kg | AUC21day | 5110 µg*h/mL | Standard Deviation 952 |
| ONO-4538 3 mg/kg | AUC21day | 12200 µg*h/mL | Standard Deviation 2060 |
| ONO-4538 10 mg/kg | AUC21day | 38700 µg*h/mL | Standard Deviation 14200 |
Primary
AUCinf
AUCinf was the area under serum concentration-time curve of ONO-4538 extrapolated to infinity.
Time frame: 3 weeks: from the start of administration to the end of treatment phase. Actual blood sampling points are pre-dose, 1hr, 3hr, 9hr, 25hr, 49hr, 73hr, 169hr, 337hr, and 504hr.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ONO-4538 1 mg/kg | AUCinf | 9180 µg*h/mL | Standard Deviation 3140 |
| ONO-4538 3 mg/kg | AUCinf | 22800 µg*h/mL | Standard Deviation 10000 |
| ONO-4538 10 mg/kg | AUCinf | 68100 µg*h/mL | Standard Deviation 34700 |
Primary
PK Outcome: Cmax of ONO-4538
Cmax was the maximum serum concentration of ONO-4538 after the single administration.
Time frame: 3 weeks: from the start of administration to the end of treatment phase. Actual blood sampling points are pre-dose, 1hr, 3hr, 9hr, 25hr, 49hr, 73hr, 169hr, 337hr, and 504hr.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ONO-4538 1 mg/kg | PK Outcome: Cmax of ONO-4538 | 26.0 µg/mL | Standard Deviation 4.29 |
| ONO-4538 3 mg/kg | PK Outcome: Cmax of ONO-4538 | 64.3 µg/mL | Standard Deviation 22.5 |
| ONO-4538 10 mg/kg | PK Outcome: Cmax of ONO-4538 | 242.0 µg/mL | Standard Deviation 66.7 |
Primary
PK Outcome: Tmax of ONO-4538
Tmax was the time to reach the Cmax.
Time frame: 3 weeks: from the start of administration to the end of treatment phase. Actual blood sampling points are pre-dose, 1hr, 3hr, 9hr, 25hr, 49hr, 73hr, 169hr, 337hr, and 504hr.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ONO-4538 1 mg/kg | PK Outcome: Tmax of ONO-4538 | 3.02 hours |
| ONO-4538 3 mg/kg | PK Outcome: Tmax of ONO-4538 | 3.00 hours |
| ONO-4538 10 mg/kg | PK Outcome: Tmax of ONO-4538 | 2.99 hours |
Primary
T1/2
T1/2 was the elimination half-life of serum concentration of ONO-4538.
Time frame: 3 weeks: from the start of administration to the end of treatment phase. Actual blood sampling points are pre-dose, 1hr, 3hr, 9hr, 25hr, 49hr, 73hr, 169hr, 337hr, and 504hr.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ONO-4538 1 mg/kg | T1/2 | 18.3 days | Standard Deviation 6.97 |
| ONO-4538 3 mg/kg | T1/2 | 19.1 days | Standard Deviation 10 |
| ONO-4538 10 mg/kg | T1/2 | 15.0 days | Standard Deviation 7.86 |
Secondary
Safety Outcome: The Number of Deaths
Number of subjects with TEAEs leading to death.
Time frame: 3 weeks: from the start of administration to the end of treatment phase.
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ONO-4538 1 mg/kg | Safety Outcome: The Number of Deaths | 1 Participants |
| ONO-4538 3 mg/kg | Safety Outcome: The Number of Deaths | 0 Participants |
| ONO-4538 10 mg/kg | Safety Outcome: The Number of Deaths | 1 Participants |
Secondary
Safety Outcome: The Number of Subjects With Overall Adverse Events
Adverse Events (AEs) were analyzed based on treatment emergent AEs (TEAEs), defined as any event not present prior to initiation of investigational product that first appeared following exposure to investigational product or any event already present that worsened relative to the pre-treatment state following exposure to investigational product.
Time frame: 3 weeks: from the start of administration to the end of treatment phase.
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ONO-4538 1 mg/kg | Safety Outcome: The Number of Subjects With Overall Adverse Events | 5 participants |
| ONO-4538 3 mg/kg | Safety Outcome: The Number of Subjects With Overall Adverse Events | 4 participants |
| ONO-4538 10 mg/kg | Safety Outcome: The Number of Subjects With Overall Adverse Events | 5 participants |