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

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

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.

Study Overview

• Status: Completed
• Conditions: Malignant Solid Tumor
• Intervention / Treatment: Biological: ONO-4538

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Kanto
    • Kanto Region, Kanto, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort	Biological: ONO-4538; 1mg/kg, 3mg/kg, 10mg/kg and 20mg/kg ONO-4538 infusion cohorts

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ono Pharmaceutical Co. Ltd
• Investigators: Study Director: Ohyama Yukiya, Ono Pharmaceutical Co. Ltd

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (ACTUAL): September 1, 2010

Study Registration Dates

• First Submitted: January 26, 2009
• First Submitted That Met QC Criteria: February 3, 2009
• First Posted (ESTIMATE): February 4, 2009

Study Record Updates

• Last Update Posted (ACTUAL): October 8, 2020
• Last Update Submitted That Met QC Criteria: September 15, 2020
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: solid tumors; ONO-4538; MDX-1106
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: ONO-4538-01