Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects
CAPTIVE
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)
1 other identifier
interventional
49
2 countries
15
Brief 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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Oct 2016
Longer than P75 for phase_2
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 9, 2016
CompletedFirst Posted
Study publicly available on registry
June 14, 2016
CompletedStudy Start
First participant enrolled
October 6, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 17, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
June 30, 2021
CompletedJuly 15, 2021
July 1, 2021
4.4 years
June 9, 2016
July 13, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Objective response rate (ORR)
Interval tumor size reduction as measured from periodic MRI
3.5 years
Secondary Outcomes (3)
Overall survival (OS)
3.5 years
Time to tumor response
3.5 years
Duration of response
3.5 years
Study Arms (1)
DNX-2401 + pembrolizumab
EXPERIMENTALIntratumoral dose (1.0 mL) of DNX-2401 followed 7-9 days later by intravenous pembrolizumab, 200 mg, given every three weeks through 105 weeks (2 yrs.) or until progressive disease or unacceptable toxicity.
Interventions
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.
Sequential intravenous administration every three weeks beginning 7-9 days after Day 0/DNX-2401
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- DNAtrix, Inc.lead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (15)
University of Arkansas for Medical Sciences (UAMS)
Little Rock, Arkansas, 72205, United States
UCLA Medical Center
Los Angeles, California, 90095, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Minnesota Neurosurgery
Minneapolis, Minnesota, 55455, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Weill-Cornell Medicine New York-Presbyterian
New York, New York, 10065, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27514, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Ohio State University James Cancer Center
Columbus, Ohio, 43210, United States
Lehigh Valley Health Network
Allentown, Pennsylvania, 18103, United States
Texas Oncology Austin-Midtown
Austin, Texas, 78705, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Huntsman Cancer Institute
Salt Lake City, Utah, 84112, United States
University Health Network
Toronto, Ontario, M5T 2S8, Canada
Related Publications (1)
Nassiri F, Patil V, Yefet LS, Singh O, Liu J, Dang RMA, Yamaguchi TN, Daras M, Cloughesy TF, Colman H, Kumthekar PU, Chen CC, Aiken R, Groves MD, Ong SS, Ramakrishna R, Vogelbaum MA, Khagi S, Kaley T, Melear JM, Peereboom DM, Rodriguez A, Yankelevich M, Nair SG, Puduvalli VK, Aldape K, Gao A, Lopez-Janeiro A, de Andrea CE, Alonso MM, Boutros P, Robbins J, Mason WP, Sonabend AM, Stupp R, Fueyo J, Gomez-Manzano C, Lang FF, Zadeh G. Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial. Nat Med. 2023 Jun;29(6):1370-1378. doi: 10.1038/s41591-023-02347-y. Epub 2023 May 15.
PMID: 37188783DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Nancy Gady, BS
DNAtrix, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 9, 2016
First Posted
June 14, 2016
Study Start
October 6, 2016
Primary Completion
March 17, 2021
Study Completion
June 30, 2021
Last Updated
July 15, 2021
Record last verified: 2021-07
Data Sharing
- IPD Sharing
- Will share
Plan to share aggregate data at completion of study