MTG201 Plus Nivolumab in Patients With Relapsed Pleural Mesothelioma

• ClinicalTrials.gov Identifier: NCT04013334
• Recruitment Status: Active, not recruiting
• First Posted: July 9, 2019
• Last Update Posted: June 16, 2022
• Sponsor: Momotaro-Gene Inc.
• Collaborators: Baylor College of Medicine; Synteract, Inc.
• Information provided by (Responsible Party): Momotaro-Gene Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Malignant Pleural Mesothelioma	Drug: MTG201; Drug: Nivolumab Injection [Opdivo]	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Single arm, open-label
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-Label, Single-Center Study of MTG201 in Combination With Nivolumab in Patients With Relapsed Malignant Pleural Mesothelioma
• Actual Study Start Date: August 15, 2019
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: January 1, 2023

Arms and Interventions

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 Name: Ad-SGE-REIC/Dkk-3; Drug: Nivolumab Injection [Opdivo]; Nivolumab 480 mg by IV infusion every 4 weeks; Other Name: Opdivo

Outcome Measures

Primary Outcome Measures :

1. Objective response rate (ORR) [ Time Frame: 3 months-2 years ]
   Percentage of subjects with complete or partial response

Secondary Outcome Measures :

1. duration of response (DUR) [ Time Frame: up to 2 years ]
   measured from first observation of response to disease progression
2. progression free survival (PFS) [ Time Frame: up to 2 years ]
   measured from start of study to date of progression or death

Other Outcome Measures:

1. Incidence of adverse events [ Time Frame: up to 2 years ]
   description of adverse events by frequency, severity and causality
2. change from baseline in liver transaminases [ Time Frame: 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Texas

Baylor College of Medicine

Houston, Texas, United States, 77030

Sponsors and Collaborators

Momotaro-Gene Inc.

Baylor College of Medicine

Synteract, Inc.

Investigators

• Principal Investigator: Bryan Burt, MD; Baylor College of Medicine Thoracic Surgery

More Information

• Responsible Party: Momotaro-Gene Inc.
• ClinicalTrials.gov Identifier: NCT04013334
• Other Study ID Numbers: MTG201-MPM-001
• First Posted: July 9, 2019
• Last Update Posted: June 16, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Mesothelioma; Mesothelioma, Malignant; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Nivolumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action