MTG201 Plus Nivolumab in Patients With Relapsed Pleural Mesothelioma

Study Overview
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Brief Summary
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Twelve patients with relapsed malignant pleural mesothelioma will be treated with intratumoral injections of MTG201, a replication incompetent adenovirus, modified by the insertion of the reduced expression in immortalized cells (REIC)/Dikkopf (Dkk)-3 gene, on Days 1, 8, 22, and 50. Patients will also receive every 4 weekly intravenous infusions of nivolumab, 480 mg, starting on Day 2. Safety and anti-tumor activity will be monitored at regular intervals throughout the study.

Detailed Description
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This is a study of the efficacy and safety of MTG201 given by intratumoral injection to patients with malignant pleural mesothelioma who have failed front line chemotherapy. Patients will also receive IV infusions of nivolumab every 4 weeks. MTG201 is a replication incompetent adenovirus into which the gene for REIC/Dkk-3 has been inserted. The insertion of this gene has been shown to endow the adenovirus with anti-tumor activity and to result in enhanced anti-tumor immunity. MTG201, 3 x 10E12 vp, will be given by intratumoral injection on days 1, 8, 22 and 50. Nivolumab, 480 mg, will be given by IV infusion every 4 weeks until progression. Efficacy will be assessed by CT scans at 4 and 12 weeks, then every 3 months. Safety will be assessed by reported adverse events, periodic laboratory assessments, physical exams, vital signs. The pharmacokinetics and pharmacodynamics of MTG201 will be assessed periodically. Tumor biopsy will be obtained on Days 1, 8 and 50 prior to MTG201 administration.

Official Title
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A Phase 2, Open-Label, Single-Center Study of MTG201 in Combination With Nivolumab in Patients With Relapsed Malignant Pleural Mesothelioma

Conditions
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Malignant Pleural Mesothelioma

Intervention / Treatment
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* Drug: MTG201
* Drug: Nivolumab Injection [Opdivo]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed locally advanced or metastatic pleural mesothelioma Failed one prior treatment regimen including cisplatin-based chemotherapy Eastern cooperative oncology group (ECOG) performance status; 0,1 Adequate organ function Measurable disease per RECIST Exclusion Criteria: Candidate for surgical resection has active autoimmune disease, primary or acquired immunodeficiency significant cardiovascular disease has active interstitial lung disease has active infection or HIV, hepatitis B or C previous anti-PD-1, PD-L1 or CTLA-4 inhibitor immunotherapy other clinical significant disorder that could affect conduct of 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
Intervention Model: Single Group Assignment
Interventional Model Description: Single arm, open-label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MTG201 plus Nivolumab<br>Single arm, open-label, patients receive both MTG201 and nivolumab | Drug: MTG201<br>* MTG201, 3 x 10E12 vp delivered by intratumoral injection on days 1, 8, 22 and 50<br>* Other names: Ad-SGE-REIC/Dkk-3;Drug: Nivolumab Injection [Opdivo]<br>* Nivolumab 480 mg by IV infusion every 4 weeks<br>* Other names: Opdivo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Percentage of subjects with complete or partial response | 3 months-2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| duration of response (DUR) | measured from first observation of response to disease progression | up to 2 years | 
| progression free survival (PFS) | measured from start of study to date of progression or death | up to 2 years |