Clinical trial NCT04013334: MTG201 Plus Nivolumab in Patients With Relapsed Pleural Mesothelioma
Official title: A Phase 2, Open-Label, Single-Center Study of MTG201 in Combination With Nivolumab in Patients With Relapsed Malignant Pleural Mesothelioma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Malignant Pleural Mesothelioma
Lead sponsor: Momotaro-Gene Inc.
Sponsor class: INDUSTRY
Collaborators: name: Baylor College of Medicine
name: Synteract, Inc.
First posted: 2019-07-09
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single arm, open-label
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: 3 months-2 years
Secondary outcomes:
measure: duration of response (DUR)
timeFrame: up to 2 years
measure: progression free survival (PFS)
timeFrame: up to 2 years
Other outcomes:
measure: Incidence of adverse events
timeFrame: up to 2 years
measure: change from baseline in liver transaminases
timeFrame: up to 2 years
Locations:
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Baylor College of Medicine Thoracic Surgery
name: Bryan Burt, MD
role: PRINCIPAL_INVESTIGATOR
References: