Study of Combination Therapy With Mogamulizumab (KW-0761) and Nivolumab (ONO-4538/BMS-936558) in Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to characterize the safety and tolerability and determine the maximum tolerated dose (MTD) or the recommended fixed dose of the combinations of Mogamulizumab and Nivolumab in subjects with locally advanced or metastatic solid tumors.

Official Title
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Phase 1 Study of Combination Therapy With Mogamulizumab (KW-0761) and Nivolumab (ONO-4538/BMS-936558) in Subjects With Advanced Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Biological: Mogamulizumab: KW-0761, Nivolumab: (ONO-4538/BMS-936558)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who voluntarily signed and dated Institutional Review Board approved informed consent form in accordance with regulatory and institutional guidelines. Subjects who have progressed or have been intolerant to any standard treatment regimen or refused standard treatment, or for which adequate standard therapy does not exist. Subjects who have evaluable lesion per guideline of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Subjects with life expectancy > 12 weeks. Subjects with Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1. Potential child-bearing female who has agreed with contraception and not breast-feeding. For male who also has agreed with contraception. Subjects who have adequate hematological, renal, hepatic and respiratory functions defined. Must agree to present archival tumor tissues to sponsor or be willing to undergo a pre-treatment biopsy. Histologically or cytologically confirmed locally advanced or metastatic solid tumors. Exclusion Criteria: Female subjects who are pregnant or breast-feeding. Subjects with uncontrolled and significant inter-current illness. Subjects with known central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects who have been previously treated with an anti-programmed death 1 (PD-1), anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. Subjects who have been previously treated with Mogamulizumab. Subjects with any prior Grade ≥ 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE. Subjects with a history of severe hypersensitivity reactions to drugs. Subjects who have been received chemotherapies, immunotherapy, biologic or hormonal therapies, another investigational drug, radiation or major surgery for cancer treatment within 28 days or 42 days (for nitrosourea or mitomycin C) prior to Cycle 1 Day 1. Subjects who have known active autoimmune disease or syndrome. Subjects who have active inflammatory bowel disease, irritable bowel disease, celiac disease, or other serious GI chronic conditions associated with diarrhea.

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: Mogamulizumab+Nivolumab<br>During parts 1 and 2, Mogamulizumab and Nivolumab are administered at appropriate intervals. Part 1 (Dose Escalation Part) During Cohort 1 to 2, Mogamulizumab and Nivolumab are administered in combination. Part 2 (Expansion Part) Patients will be treated with maximum tolerated dose established in the dose escalation part for each combination. | Biological: Mogamulizumab: KW-0761, Nivolumab: (ONO-4538/BMS-936558)<br>* i.v. administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects reporting adverse events |  | From the first dose of study medications until 90 days after the last dose of study medication | 
| Number of subjects reporting serious adverse events |  | From the first dose of study medications until 90 days after the last dose of study medication | 
| Percentage of subjects reporting serious adverse events |  | From the first dose of study medications until 90 days after the last dose of study medication | 
| Percentage of subjects reporting adverse events |  | From the first dose of study medications until 90 days after the last dose of study medication | 
| Number of subjects experiencing dose-limiting toxicity |  | For 28 days from the first dose of study medications |