ONO-4538 Phase I Study in Patients With Advanced Malignant Solid Tumors in Japan

Study Overview
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Brief Summary
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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.

Official Title
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ONO-4538 Phase I Study - A Single Center, Open Label, Dose Escalation Single Dose, Followed by Multiple Dose Study of ONO-4538, a Fully Human mAb to PD-1, in Patients With Advanced Malignant Solid Tumors

Conditions
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Malignant Solid Tumor

Intervention / Treatment
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* Biological: ONO-4538


Participation Criteria
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Eligibility Criteria
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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 exclusion criteria as specified in the study protocol

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort<br> | Biological: ONO-4538<br>* 1mg/kg, 3mg/kg, 10mg/kg and 20mg/kg ONO-4538 infusion cohorts<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Ceoi：Serum concentrations immediately after the end of continuous administration | day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | up to study completion, every 4 weeks in principle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ONO-4538, MDX-1106, solid tumors