Safety and Efficacy of MIW815 (ADU-S100) +/- Ipilimumab in Patients With Advanced/Metastatic Solid Tumors or Lymphomas

Study Overview
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Brief Summary
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The purpose of this study is to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics and antitumor activity of MIW815 (ADU-S100) administered via intratumoral injection as a single agent and in combination with ipilimumab.

Official Title
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A Phase I, Open Label, Multicenter Study of the Safety and Efficacy of MIW815 (ADU-S100) Administered by Intratumoral Injection to Patients With Advanced/Metastatic Solid Tumors or Lymphomas

Conditions
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Advanced/Metastatic Solid Tumors or Lymphomas

Intervention / Treatment
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* Drug: ADU-S100
* Biological: ipilimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ECOG ≤ 1 Willing to undergo tumor biopsies from injected and distal lesions Must have two biopsy accessible lesions: * one lesion must be ≥10 mm and <100 mm in longest diameter, accessible for repeated intratumoral (IT) injection and accessible for baseline and on-treatment biopsies. a second (distal) lesion must be accessible for baseline and on-treatment biopsy and must be distinct from the injected lesion. tumors encasing major vascular structures (i.e., carotid artery or tumors close to other vital organs), are not considered appropriate Exclusion Criteria: Patients who require local palliative measures such as XRT or surgery Symptomatic or untreated leptomeningeal disease. Presence of symptomatic central nervous system (CNS) metastases Impaired cardiac function or clinically significant cardiac disease Active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved childhood asthma/atopy. Active infection requiring systemic antibiotic therapy. Known history of Human Immunodeficiency Virus (HIV) infection. Active Epstein-Barr virus (EBV), hepatitis B virus (HBV) or hepatitis C virus (HCV) Malignant disease, other than that being treated in this study.

Ages Eligible for Study
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Minimum Age: 18 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: Dose escalation monotherapy<br>ADU-S100 administered intratumorally on Days 1, 8 and 15 of each 28-day cycle until unacceptable toxicity, progressive disease and/or treatment is discontinued; starting dose 50 micrograms | Drug: ADU-S100<br> <br> * Other names: MIW815;|
| Experimental: Dose escalation combination<br>ADU-S100 administered intratumorally on Days 1 and 8 of each 21-day cycle (starting dose 200 micrograms) and ipilimumab, i.v., (3 mg/kg) on day 1 of each 21-day cycle for the first 4 cycles. Dosing is continued until unacceptable toxicity, progressive disease and/or treatment is discontinued | Drug: ADU-S100<br> <br> * Other names: MIW815;Biological: ipilimumab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Number of patients reporting treatment-related adverse events that qualify as dose-limiting toxicities | Number of patients reporting treatment-related adverse events that qualify as dose-limiting toxicities | 6 months from study start | 
| Recommended dose | Using maximum tolerated dose to identify the recommended dose for future studies | 6 months from study start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics measured through plasma concentrations | measured through plasma concentrations | 6 months from study start | 
| measurement of CD8-TIL counts |  | 6 months from study start | 
| RNA expression analysis of IFN gamma and immunomodulatory genes |  | 6 months from study start |