Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects

Glioblastoma Clinical Trial

— CAPTIVE  

Official title:

A Phase II, Multi-center, Open-label Study of a Conditionally Replicative Adenovirus (DNX-2401) With Pembrolizumab (KEYTRUDA®) for Recurrent Glioblastoma or Gliosarcoma (CAPTIVE/KEYNOTE-192)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02798406
• Other study ID #: 2401BT-002P
• Status: Completed
• Phase: Phase 2
• Start date: October 6, 2016
• Est. completion date: June 30, 2021

Study information

• Verified date: July 2021
• Source: DNAtrix, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Glioblastoma (GBM) and gliosarcoma (GS) are the most common and aggressive forms of malignant brain tumor in adults and can be resistant to conventional therapies. The purpose of this Phase II study is to evaluate how well a recurrent glioblastoma or gliosarcoma tumor responds to one injection of DNX-2401, a genetically modified oncolytic adenovirus, when delivered directly into the tumor followed by the administration of intravenous pembrolizumab (an immune checkpoint inhibitor) given every 3 weeks for up to 2 years or until disease progression.

Funding Source-FDA OOPD

Description:

In the initial phase of the study, up to 12 evaluable subjects will be enrolled in 3 dose cohorts to determine the best dose of DNX-2401, as follows:

• Cohort 1: Single dose DNX-2401 (5e8 vp) delivered intratumorally by cannula, followed by intravenous pembrolizumab every 3 weeks (Q3W)

• Cohort 2: Single dose DNX-2401(5e9 vp) delivered intratumorally by cannula, followed by intravenous pembrolizumab every 3 weeks (Q3W)

• Cohort 3: Single dose DNX-2401 (5e10 vp) delivered intratumorally by cannula, followed by intravenous pembrolizumab every 3 weeks (Q3W)

Following the initial phase, up to 36 additional subjects diagnosed with recurrent glioblastoma or gliosarcoma will be enrolled to receive a single of DNX-2401 determined in the initial phase administered intratumorally followed by intravenous pembrolizumab every 3 weeks.

All subjects will return to the clinic for study follow-up visits at regular intervals for safety monitoring, MRI scans and other assessments, for up to 2 years or until disease progression. All subjects will be followed closely for safety and survival.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: June 30, 2021
• Est. primary completion date: March 17, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• A single glioblastoma or gliosarcoma tumor with histopathological confirmation for first or presenting second recurrence of glioblastoma or gliosarcoma at the time of consent

• Gross total or partial tumor resection is not possible or not planned

• A single measurable tumor that is at least 10.0 mm longest diameter (LDi) X 10.0 mm shortest diameter (SDi) and this tumor does not exceed 40.0 mm in LDi or SDi on Screening MRI

• Tumor recurrence or progression documented after previously failing surgical resection, chemotherapy or radiation

• Karnofsky performance status = 70 %

• Prior anti-tumor therapies must have been completed within time periods specified in the protocol prior to DNX-2401 injection and toxic side effects must be mild, if present

• Demonstrate adequate organ function via specified laboratory test results

Exclusion Criteria:

• Multiple (= 2) separate enhancing tumors

• Tumor location on both sides of the brain and/or involvement that would present the risk of injecting DNX-2401 into the ventricles of the brain

• Tumor location in the brain stem

• Requires or, based upon history, may require treatment with high-dose systemic corticosteroids within 2 weeks of the start of intravenous pembrolizumab infusions and within 2 weeks following the first infusion of pembrolizumab

• Uncontrolled blood-sugar levels defined as HbA1c > 7%

• Previous treatment with any checkpoint inhibitor such as anti-PD1 or PD-L1 agents including pembrolizumab (KEYTRUDA) or any other checkpoint inhibitor(s) (e.g., ipilimumab, nivolumab, etc.)

• History of (non-infectious) or current active pneumonitis that required steroids and/or a history of interstitial lung disease

• Prior gene transfer therapy or prior therapy with a cytolytic virus of any type

• Brain tumor that is not measurable on MRI or persons who are unable to have MRIs

• Pregnant or nursing females

Note: Other protocol-defined inclusion and exclusion criteria may apply as outlined in the relevant protocol version

Related Conditions & MeSH terms

• Adenoviridae Infections
• Brain Cancer
• Brain Neoplasm
• Brain Neoplasms
• Glioblastoma
• Glioma
• Gliosarcoma
• Malignant Brain Tumor
• Neoplasm by Histologic Type
• Neoplasm, Nerve Tissue
• Neoplasm, Neuroepithelial
• Neoplasms
• Neoplasms by Histologic Type
• Neoplasms, Nerve Tissue
• Neoplasms, Neuroepithelial
• Nervous System Diseases
• Neuroectodermal Tumors
• Neuroectodermal Tumors, Primitive

Intervention

Biological:
• DNX-2401
On Day 0, following brain tumor biopsy and confirmation of recurrent tumor, a single injection of DNX-2401 is administered directly into the brain tumor.
• pembrolizumab
Sequential intravenous administration every three weeks beginning 7-9 days after Day 0/DNX-2401

Locations

Country	Name	City	State
Canada	University Health Network	Toronto	Ontario
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	Texas Oncology Austin-Midtown	Austin	Texas
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Ohio State University James Cancer Center	Columbus	Ohio
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Arkansas for Medical Sciences (UAMS)	Little Rock	Arkansas
United States	UCLA Medical Center	Los Angeles	California
United States	University of Minnesota Neurosurgery	Minneapolis	Minnesota
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill-Cornell Medicine New York-Presbyterian	New York	New York
United States	Huntsman Cancer Institute	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
DNAtrix, Inc.	Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR)	Interval tumor size reduction as measured from periodic MRI	3.5 years
Secondary	Overall survival (OS)	Months alive following treatment as measured during periodic study visits	3.5 years
Secondary	Time to tumor response	Months to response following treatment as measured during periodic MRIs	3.5 years
Secondary	Duration of response	Months of sustained response as measured during periodic study visits	3.5 years