Study of Pre-operative Combination Therapy With Mogamulizumab and Nivolumab Against Solid Cancer Patients

Study Overview
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Brief Summary
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To assess the safety of preoperative combination therapy with KW-0761 (anti-CCR4) and ONO-4538 (anti-PD-1). To assess the behavior of immune cells in peripheral blood and tumor.

Official Title
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Phase I Study of Pre-operative Combination Therapy With Mogamulizumab (Anti-CCR4) and Nivolumab (Anti-PD-1) Against Solid Cancer Patients

Conditions
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Gastric Cancer, Esophageal Cancer, Lung Cancer, Renal Cancer, Oral Cancer

Intervention / Treatment
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* Biological: Mogamulizumab
* Biological: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who enable to have standard operation Patients who refuse standard preoperative chemotherapy and are diagnosed with following cancers; gastric adenocarcinoma, esophageal squamous cell carcinoma, non-small-cell lung carcinoma, renal cell carcinoma or oral squamous cell carcinoma Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Patients with no serious disorder of major organs (born marrow, heart, lung, liver and kidney) Patients with written informed consent Patients who have measurable target lesion Patients who are enable to undergo biopsy for sampling tumor tissue Exclusion Criteria: Known or previous autoimmune disease Known or suspected interstitial lung disease (ILD) Patients with history of serious anaphylaxis induced by antibody preparation Uncontrollable hypertension Uncontrollable endocrine disease Patients who have active inflammatory bowel disease or other serious GI chronic conditions associated with diarrhea Uncontrollable diabetes Prior therapy with sustained anticancer agents, radiotherapy or surgery for primary disease Pregnant or lactating females, female and male patients who cannot agree to practice the adequate birth control after the consent during the study Known or suspected infection or inflammatory disease Prior therapy with hematopoietic stem cell transplantation Known or suspected central nervous system (CNS) involvement

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>KW-0761 (Mogamulizumab): 0.1 mg/kg, every week, 4 times ONO-4538 (Nivolumab): 3.0 mg/kg, every two weeks, 3 times | Biological: Mogamulizumab<br>* Mogamulizumab (0.1, 0.3 or 1.0 mg/kg) is administered.<br>* Other names: KW-0761;Biological: Nivolumab<br>* Nivolumab (3.0 mg/kg) is administered.<br>* Other names: ONO-4538;|
| Experimental: Cohort 2<br>KW-0761 (Mogamulizumab): 0.3 mg/kg, every week, 4 times ONO-4538 (Nivolumab): 3.0 mg/kg, every two weeks, 3 times | Biological: Mogamulizumab<br>* Mogamulizumab (0.1, 0.3 or 1.0 mg/kg) is administered.<br>* Other names: KW-0761;Biological: Nivolumab<br>* Nivolumab (3.0 mg/kg) is administered.<br>* Other names: ONO-4538;|
| Experimental: Cohort 3<br>KW-0761 (Mogamulizumab): 1.0 mg/kg, every week, 4 times ONO-4538 (Nivolumab): 3.0 mg/kg, every two weeks, 3 times | Biological: Mogamulizumab<br>* Mogamulizumab (0.1, 0.3 or 1.0 mg/kg) is administered.<br>* Other names: KW-0761;Biological: Nivolumab<br>* Nivolumab (3.0 mg/kg) is administered.<br>* Other names: ONO-4538;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events including intraoperative and postoperative complications | Confirm the toxicity profile, which is measured by the degree of grade and seriousness, duration, causality, classification, etc. of the adverse events. | from first administration to 60 days after the final administration or to 30 days after the standard operation | 
| Rate of Foxp3-positive patients in tumor by immunohistochemical analysis |  | from baseline until standard operation, an average of 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective tumor response rate according to RECIST v1.1 |  | from baseline to 6 weeks after the first administration | 
| Rate of Treg decrease in peripheral blood mononuclear cell (PBMC) |  | from baseline to 60 days after the final administration or to 30 days after the standard operation |