MTG201 Plus Nivolumab in Patients With Relapsed Pleural Mesothelioma

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Malignant Pleural Mesothelioma
• Intervention / Treatment: Drug: MTG201; Drug: Nivolumab Injection [Opdivo]

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	description of adverse events by frequency, severity and causality	up to 2 years
change from baseline in liver transaminases	changes in liver transaminases from prior to first study drug treatment to various timepoints throughout the treatment and follow-up period	up to 2 years

Collaborators and Investigators

• Sponsor: Momotaro-Gene Inc.
• Collaborators: Baylor College of Medicine; Synteract, Inc.
• Investigators: Principal Investigator: Bryan Burt, MD, Baylor College of Medicine Thoracic Surgery

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2019
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: May 24, 2019
• First Submitted That Met QC Criteria: July 8, 2019
• First Posted (Actual): July 9, 2019

Study Record Updates

• Last Update Posted (Actual): June 16, 2022
• Last Update Submitted That Met QC Criteria: June 13, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Mesothelioma; Mesothelioma, Malignant; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: MTG201-MPM-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No