Malignant Solid Tumor
Conditions
Keywords
ONO-4538, MDX-1106, solid tumors
Brief summary
Evaluation of the safety, tolerability and pharmacokinetics (PK) of a single dose and multiple doses of ONO-4538 in Japanese patients with advanced malignant solid tumors, and exploratory evaluation of the pharmacological effect and efficacy of ONO-4538.
Interventions
BIOLOGICALONO-4538
1mg/kg, 3mg/kg, 10mg/kg and 20mg/kg ONO-4538 infusion cohorts
Sponsors
Ono Pharmaceutical Co. Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological or cytological diagnosis of solid tumor with at least one measurable lesion of ≥ 10mm. * Tumor must be advanced or recurrent which is refractory to standard therapies or for which no alternative, appropriate therapy exists. * ECOG Performance Status of 0-1 * Life expectancy ≥ 3 months * Other inclusion criteria as specified in the study protocol
Exclusion criteria
* History of severe hypersensitivity reactions to other antibodies. * Residual adverse reactions or effect of prior therapy, which deemed to affect the safety evaluation of the study drug by the investigator or subinvestigator. * Two or more synchronous tumors, except for adequately treated basal cell cancer or cancer in situ, or superficial bladder cancer, or any other cancers from which the patient has been disease-free for at least 5 years. * Patients with any active autoimmune disease or a documented history of chronic or recurrent autoimmune disease, or current medical condition that requires systemic immunosuppressive doses of steroids or other immunosuppressive medications. * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax at Single Dose | day1(before administration, 1 hour after the start of administration, and 2 and 8 hours after the end of administration), day2(24 h), day3(48 h), day4(72 h), day8, day15, and day22 or at the discontinuation | — |
| AUClast at Single Dose | day1(before administration, 1 hour after the start of administration, and 2 and 8 hours after the end of administration), day2(24 h), day3(48 h), day4(72 h), day8, day15, and day22 or at the discontinuation | — |
| T1/2 at Single Dose | day1(before administration, 1 hour after the start of administration, and 2 and 8 hours after the end of administration), day2(24 h), day3(48 h), day4(72 h), day8, day15, and day22 or at the discontinuation | — |
| Ceoi at Multiple Doses | day 15 | Ceoi：Serum concentrations immediately after the end of continuous administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response | up to study completion, every 4 weeks in principle | Response Evaluation Criteria In Solid Tumors Criteria (ver 1.0) was used for this Outcome Measure. Please see the reference for the detailed description. Therasse, Arbuck et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000;92:205-16. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ONO-4538 1mg/kg Cohorts Administer ONO-4538 1mg/kg as an intravenous infusion over ≥1 hour | 3 |
| ONO-4538 3mg/kg Cohorts Administer ONO-4538 3mg/kg as an intravenous infusion over ≥1 hour | 5 |
| ONO-4538 10mg/kg Cohorts Administer ONO-4538 10mg/kg as an intravenous infusion over ≥1 hour | 6 |
| ONO-4538 20mg/kg Cohorts Administer ONO-4538 20mg/kg as an intravenous infusion over ≥1 hour | 3 |
| Total | 17 |
Baseline characteristics
| Characteristic | ONO-4538 1mg/kg Cohorts | ONO-4538 3mg/kg Cohorts | ONO-4538 10mg/kg Cohorts | ONO-4538 20mg/kg Cohorts | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 4 Participants | 5 Participants | 1 Participants | 11 Participants |
| Cancer treatment history (drug therapy) None | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Cancer treatment history (drug therapy) Present | 3 Participants | 5 Participants | 5 Participants | 3 Participants | 16 Participants |
| Cancer treatment history (radiotherapy) None | 3 Participants | 3 Participants | 4 Participants | 2 Participants | 12 Participants |
| Cancer treatment history (radiotherapy) Present | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Cancer treatment history (surgery) None | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Cancer treatment history (surgery) Present | 3 Participants | 4 Participants | 4 Participants | 1 Participants | 12 Participants |
| disease stage classification IV | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 4 Participants |
| disease stage classification IVb | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| disease stage classification Recurrent | 3 Participants | 2 Participants | 4 Participants | 2 Participants | 11 Participants |
| Performance Status（ECOG） 0 | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 4 Participants |
| Performance Status（ECOG） 1 | 2 Participants | 4 Participants | 4 Participants | 3 Participants | 13 Participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 0 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 6 Participants | 2 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 5 | 0 / 6 | 0 / 3 |
| other Total, other adverse events | 3 / 3 | 5 / 5 | 6 / 6 | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 | 1 / 5 | 2 / 6 | 0 / 3 |
Outcome results
Primary
AUClast at Single Dose
Time frame: day1(before administration, 1 hour after the start of administration, and 2 and 8 hours after the end of administration), day2(24 h), day3(48 h), day4(72 h), day8, day15, and day22 or at the discontinuation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ONO-4538 1mg/kg Cohorts | AUClast at Single Dose | 4950 μg·h/mL | Standard Deviation 580 |
| ONO-4538 3mg/kg Cohorts | AUClast at Single Dose | 12300 μg·h/mL | Standard Deviation 4500 |
| ONO-4538 10mg/kg Cohorts | AUClast at Single Dose | 43900 μg·h/mL | Standard Deviation 7200 |
| ONO-4538 20mg/kg Cohorts | AUClast at Single Dose | 67400 μg·h/mL | Standard Deviation 15500 |
Primary
Ceoi at Multiple Doses
Ceoi：Serum concentrations immediately after the end of continuous administration
Time frame: day 15
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ONO-4538 1mg/kg Cohorts | Ceoi at Multiple Doses | 29.3 μg/mL | Standard Deviation 6 |
| ONO-4538 3mg/kg Cohorts | Ceoi at Multiple Doses | 101 μg/mL | Standard Deviation 12 |
| ONO-4538 10mg/kg Cohorts | Ceoi at Multiple Doses | 270 μg/mL | Standard Deviation 42 |
| ONO-4538 20mg/kg Cohorts | Ceoi at Multiple Doses | 286 μg/mL | Standard Deviation 112 |
Primary
Cmax at Single Dose
Time frame: day1(before administration, 1 hour after the start of administration, and 2 and 8 hours after the end of administration), day2(24 h), day3(48 h), day4(72 h), day8, day15, and day22 or at the discontinuation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ONO-4538 1mg/kg Cohorts | Cmax at Single Dose | 24.4 μg/mL | Standard Deviation 4.5 |
| ONO-4538 3mg/kg Cohorts | Cmax at Single Dose | 68.8 μg/mL | Standard Deviation 10.9 |
| ONO-4538 10mg/kg Cohorts | Cmax at Single Dose | 192 μg/mL | Standard Deviation 36 |
| ONO-4538 20mg/kg Cohorts | Cmax at Single Dose | 214 μg/mL | Standard Deviation 68 |
Primary
T1/2 at Single Dose
Time frame: day1(before administration, 1 hour after the start of administration, and 2 and 8 hours after the end of administration), day2(24 h), day3(48 h), day4(72 h), day8, day15, and day22 or at the discontinuation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ONO-4538 1mg/kg Cohorts | T1/2 at Single Dose | 15 day | Standard Deviation 0 |
| ONO-4538 3mg/kg Cohorts | T1/2 at Single Dose | 13 day | Standard Deviation 7 |
| ONO-4538 10mg/kg Cohorts | T1/2 at Single Dose | 21 day | Standard Deviation 11 |
| ONO-4538 20mg/kg Cohorts | T1/2 at Single Dose | 17 day | Standard Deviation 9 |
Secondary
Best Overall Response
Response Evaluation Criteria In Solid Tumors Criteria (ver 1.0) was used for this Outcome Measure. Please see the reference for the detailed description. Therasse, Arbuck et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000;92:205-16.
Time frame: up to study completion, every 4 weeks in principle
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ONO-4538 1mg/kg Cohorts | Best Overall Response | CR | 0 Participants |
| ONO-4538 1mg/kg Cohorts | Best Overall Response | Unknown | 0 Participants |
| ONO-4538 1mg/kg Cohorts | Best Overall Response | PD | 2 Participants |
| ONO-4538 1mg/kg Cohorts | Best Overall Response | PR | 1 Participants |
| ONO-4538 1mg/kg Cohorts | Best Overall Response | SD | 0 Participants |
| ONO-4538 3mg/kg Cohorts | Best Overall Response | Unknown | 0 Participants |
| ONO-4538 3mg/kg Cohorts | Best Overall Response | PR | 0 Participants |
| ONO-4538 3mg/kg Cohorts | Best Overall Response | SD | 1 Participants |
| ONO-4538 3mg/kg Cohorts | Best Overall Response | PD | 3 Participants |
| ONO-4538 3mg/kg Cohorts | Best Overall Response | CR | 1 Participants |
| ONO-4538 10mg/kg Cohorts | Best Overall Response | Unknown | 0 Participants |
| ONO-4538 10mg/kg Cohorts | Best Overall Response | SD | 2 Participants |
| ONO-4538 10mg/kg Cohorts | Best Overall Response | CR | 0 Participants |
| ONO-4538 10mg/kg Cohorts | Best Overall Response | PD | 3 Participants |
| ONO-4538 10mg/kg Cohorts | Best Overall Response | PR | 1 Participants |
| ONO-4538 20mg/kg Cohorts | Best Overall Response | PR | 0 Participants |
| ONO-4538 20mg/kg Cohorts | Best Overall Response | PD | 3 Participants |
| ONO-4538 20mg/kg Cohorts | Best Overall Response | Unknown | 0 Participants |
| ONO-4538 20mg/kg Cohorts | Best Overall Response | SD | 0 Participants |
| ONO-4538 20mg/kg Cohorts | Best Overall Response | CR | 0 Participants |