Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects (CAPTIVE)

• ClinicalTrials.gov Identifier: NCT02798406
• Recruitment Status: Completed
• First Posted: June 14, 2016
• Last Update Posted: July 15, 2021
• Sponsor: DNAtrix, Inc.
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): DNAtrix, Inc.

Tracking Information

• First Submitted Date: June 9, 2016
• First Posted Date: June 14, 2016
• Last Update Posted Date: July 15, 2021
• Actual Study Start Date: October 6, 2016
• Actual Primary Completion Date: March 17, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 13, 2016)

Objective response rate (ORR) [ Time Frame: 3.5 years ]

Interval tumor size reduction as measured from periodic MRI

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 13, 2016)

• Overall survival (OS) [ Time Frame: 3.5 years ]
  Months alive following treatment as measured during periodic study visits
• Time to tumor response [ Time Frame: 3.5 years ]
  Months to response following treatment as measured during periodic MRIs
• Duration of response [ Time Frame: 3.5 years ]
  Months of sustained response as measured during periodic study visits

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects
• 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)

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

Detailed 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

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.
  Other Names:

  • Oncolytic virus
  • Genetically-modified adenovirus
  • Delta-24
  • Delta-24-RGD
• Biological: pembrolizumab
  Sequential intravenous administration every three weeks beginning 7-9 days after Day 0/DNX-2401
  Other Names:

  • KEYTRUDA
  • lambrolizumab
  • MK-3475
  • SCH 900475
  • Checkpoint inhibitor
  • monoclonal antibody
  • anti-PD1/PD-L1

Study Arms

Experimental: DNX-2401 + pembrolizumab

Intratumoral 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:

• Biological: DNX-2401
• Biological: pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 20, 2019): 49
• Original Estimated Enrollment (submitted: June 13, 2016): 48
• Actual Study Completion Date: June 30, 2021
• Actual Primary Completion Date: March 17, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT02798406
• Other Study ID Numbers: 2401BT-002P
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Plan to share aggregate data at completion of study

• Current Responsible Party: DNAtrix, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: DNAtrix, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC

Investigators

• Study Director: Nancy Gady, BS; DNAtrix, Inc.

• PRS Account: DNAtrix, Inc.
• Verification Date: July 2021