Malignant Pleural Mesothelioma
Conditions
Brief summary
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
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.
Interventions
DRUGMTG201
MTG201, 3 x 10E12 vp delivered by intratumoral injection on days 1, 8, 22 and 50
Nivolumab 480 mg by IV infusion every 4 weeks
Sponsors
Baylor College of Medicine
Synteract, Inc.
Momotaro-Gene Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single arm, open-label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | 3 months-2 years | Percentage of subjects with complete or partial response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| duration of response (DUR) | up to 2 years | measured from first observation of response to disease progression |
| progression free survival (PFS) | up to 2 years | measured from start of study to date of progression or death |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events | up to 2 years | description of adverse events by frequency, severity and causality |
| change from baseline in liver transaminases | up to 2 years | changes in liver transaminases from prior to first study drug treatment to various timepoints throughout the treatment and follow-up period |
Countries
United States
Outcome results
None listed