Newly Diagnosed MGMT Unmethylated GlioblastomaPhase 1/2NCT05734560
D2C7-IT and 2141-V11 in Newly Diagnosed GBM Patients
A Phase 1/2 study testing D2C7-IT and 2141-V11 in people with Newly Diagnosed MGMT Unmethylated Glioblastoma, run by Darell Bigner at 1 site in United States.
Trial summary
The purpose of this research study is to determine the safety and efficacy of administering a single intracerebral (within the brain) dose of investigational compounds called D2C7-immunotoxin (IT) and 2141-V11 in residual disease (within tumor margins) after surgery, followed by later repeated injections of 2141-V11… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Newly Diagnosed MGMT Unmethylated Glioblastoma
- What is being tested?
- D2C7-IT and 2141-V11
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Sep 2023to 31 Oct 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years of age at the time of entry into the study
- Newly diagnosed supratentorial GBM, WHO grade 4, IDH wildtype, MGMT unmethylated (high grade glioma with molecular features of GBM will be eligible under WHO 4 malignant glioma) with residual radiographic non-contrast enhancing disease on the post-2 cycles of adjuvant TMZ MRI amenable to catheter placement. The residual radiographic contrast enhancing disease is ≤ 3 cm in maximal diameter in any plane.
- Patient must have completed standard of care radiation therapy (typically 59.4-60 Gy over approximately 6 weeks duration if under 65 years old and a minimum of 40 Gy over 3 weeks duration if 65 years or older) in combination with TMZ and 2 cycles of post-radiation, adjuvant TMZ. For patients known to be MGMT promoter unmethylated prior to start of radiation therapy, patients are not mandated to have received TMZ in combination to radiation therapy prior to participating in this trial.
- Karnofsky Performance Score (KPS) > 70%
- Able to undergo brain MRI wiht and without contrast
- Hemoglobin ≥ 9 g/dl prior to catheter placement
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- Platelet count ≥ 100,000/µL unsupported. Because of risks of intracranial hemorrhage with catheter placement, platelet count ≥ 125,000/µl is required for the patient to undergo biopsy and catheter insertion, which can be attained with the help of platelet transfusion
- Neutrophil count ≥ 1000 prior to catheter placement
- Creatinine ≤ 1.5 x normal range prior to catheter placement
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) prior to catheter placement (Exception: Participant has known or suspected Gilbert's Syndrome for which additional lab testing of direct and/or indirect bilirubin supports this diagnosis. In these instances, a total bilirubin of ≤ 3.0 x ULN is acceptable.)
- AST/ALT ≤ 2.5 x ULN
- PT and PTT ≤ 1.2 x normal prior to biopsy. Patients with prior history of thrombosis/embolism are allowed to be on anticoagulation, understanding that anticoagulation will be held in the perioperative period per the neurosurgical team's recommendations. Low molecular weight heparin (LMWH) is preferred. If a patient is on warfarin, the international normalized ratio (INR) is to be obtained and value should be below 2.0 prior to biopsy.
- Patient or partner(s) meets one of the following criteria:
- Non-childbearing potential (i.e. not sexually active, physiologically incapable of becoming pregnant, including any person who is post-menopausal or surgically sterile, or any person who has had a vasectomy). Surgically sterile people are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Postmenopausal for purposes of this study is defined as 1 year without menses.; or
- Childbearing potential and agrees to use one of the following methods of birth control: approved hormonal contraceptives (e.g. birth control pills, patches, implants, or infusions), an intrauterine device, or a barrier method of contraception (e.g. a condom or diaphragm) used with spermicide
- A signed ICF approved by the IRB will be required for patient enrollment into the study. Patients must be able to read and understand the informed consent document and must sign the informed consent indicating that they are aware of the investigational nature of this study
Who cannot join
- Patients who are pregnant or breast-feeding/chestfeeding
- Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons or their designate
- Patients with severe, active comorbidity, defined as follows:
- Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax > 99.5°F/37.5°C)
- Patients with known immunosuppressive disease or known human immunodeficiency virus infection
- Patients with unstable or severe medical conditions such as severe heart disease (New York Heart Association Class 3 or 4)
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- Patients with known lung (forced expiratory volume in the first second of expiration (FEV1) < 50%) disease
- Patients with uncontrolled diabetes mellitus
- Patients with albumin allergy
- Patients with known HIV or Hepatitis C positive status
- Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy
- Patients who previously received other therapeutic interventions for newly diagnosed GBM with the exception of surgical resection and standard of care concomitant radiation therapy and TMZ and 2 cycles of post-radiation, adjuvant TMZ for their brain tumor
- Patients who have received concomitant radiation therapy and TMZ ≤ 11 weeks prior to start of D2C7-IT CED infusion
- Patients with evidence of tumor in the brainstem, cerebellum, or spinal cord, radiological evidence of (actively growing) multifocal disease, tumor crossing the midline, extensive subependymal disease, or leptomeningeal disease
- Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to the start of D2C7-IT infusion
- Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups)
- Patients with prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
- Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months
- Patients who cannot undergo MRI due to obesity or to having certain metal in their bodies (i.e. pacemakers, infusion pumps, metal aneurysm clips, metal prostheses, joints, rods, or plates) or patients with any known severe allergies to contrast agents. Patients with mild allergies (i.e., rash only) are allowed to enroll and will be pretreated with acetaminophen and diphenhydramine prior to injection of the contrast agent.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27710
Annick Desjardins, MD, 919-684-5301, dukebrain1@dm.duke.edu
Stevie Threatt, 919-684-5301, dukebrain1@dm.duke.edu
About this study
Official title: Delivery of D2C7-IT and 2141-V11 Combination Immunotherapy in Residual Disease for Adult Patients With Newly Diagnosed MGMT Unmethylated Glioblastoma and Perilymphatic Subcutaneous Injections of 2141-V11
The purpose of this research study is to determine the safety and efficacy of administering a single intracerebral (within the brain) dose of investigational compounds called D2C7-immunotoxin (IT) and 2141-V11 in residual disease (within tumor margins) after surgery, followed by later repeated injections of 2141-V11 in the subcutaneous area (under the skin) around the lymph nodes of the head and neck for adults newly diagnosed with a type of cancerous brain tumor called glioblastoma. The word "investigational" means the study drugs are still being tested in research studies and are not approved by the U.S. Food and Drug Administration (FDA).
Read the detailed description
Within this study, approximately 50 study participants will receive a single infusion of D2C7-IT in the hospital, which is delivered to the tumor margins over 3 days through a catheter placed in the brain, followed by a single infusion of 2141-V11 delivered over 7 hours to the tumor margins through the same catheter. About 2 weeks after intratumoral infusion of D2C7-IT and 2141-V11, participants will have their first subcutaneous (under the skin) injection of 2141-V11 in the area around the lymph nodes of the head and neck on the same side as the tumor. About a week after this injection, participants will start standard radiation therapy (RT), which typically lasts either 3 weeks or 6 weeks depending upon age. Once RT is finished, participants will resume injections in the area around the lymph nodes of the head and neck on the same side as the tumor of 2141-V11 about 1 week later. They will have another injection about 3 weeks after finishing RT and then start a schedule of injections about every 3 weeks for up to a year.
There are risks to the study drugs that are described in this document. Some common risks related to D2C7-IT include: effects related to tumor cells dying (tumor necrosis), effects on normal brain tissue, effects related to catheter placement and removal, effects related to fluid infusion into the brain (intracerebral infusion), and reactions to the D2C7-IT being directly infused in your brain. Risks of 2141-V11 being directly infused in your brain and injected in the area around the lymph nodes of the head and neck could include: cytokine release syndrome (release of immune system cells called cytokines that can cause fever, chills, headache, muscle pain, itching, rash, chest tightness, palpitations, shortness of breath, low blood pressure, nausea, vomiting), swelling and redness in the neck area, overstimulation of your immune system such that it attacks other tissues in your body, elevated liver enzymes, and low platelets in the blood.
- Being tested
- D2C7-IT, 2141-V11
- Keywords
- D2C7, D2C7-IT, 2141-V11, Pro00110119, GBM, Glioblastoma, convection-enhanced delivery, CED, MGMT unmethylated
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D2C7-ITDrug
D2C7-IT will be dosed at 166,075 ng in 36 mL.
2141-V11Drug
2141-V11 will be dosed at 3 mg in 3.5 mL for CED administration. 2141-V11 in the cervical perilymphatic subcutaneous area will be dosed at 2 mg.
| Study group | Role | What they receive |
|---|---|---|
| D2C7-IT + 2141-V11 | Experimental | Single D2C7-IT intratumoral infusion (6920 ng/mL in 36 mL) over 72 hours followed by single 2141-V11 infusion (5 dose levels) over 7 hours followed by an injection of 2141-V11 in the cervical perilymphatic subcutaneous area ipsilateral to the tumor at week 2, radiation, and further injections of 2141-V11 in the cervical perilymphatic subcutaneous area ipsilateral to the tumor. Receives: Drug: D2C7-IT; Drug: 2141-V11 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median survival defined as the time between initiation of treatment with D2C7-IT in combination with 2141-V11 and death, or last follow up if alive.
Measured: 3 years
Secondary outcomes (4)
Safety as measured by the proportion of patients with unacceptable adverse events due to the combination of D2C7-IT and 2141-V11 administered via CED
Measured: 6 months
Safety as measured by the proportion of patients with unacceptable adverse events due to pre-radiation therapy administration of cervical perilymphatic injections of 2141-V11, or delayed completion of radiation therapy
Measured: 6 months
Safety as measured by 6-month progression-free survival (PFS6)
Measured: 6 months
Median PFS will be reported, which is defined as the median time between initiation of D2C7-IT and 2141-V11 infusion treatment and initial failure (disease progression or death).
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2023
- Study start6 Sep 2023
- Primary completion31 Oct 2026 (estimated)
- Study completion31 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Newly Diagnosed MGMT Unmethylated GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Darell Bigner
- Sponsor type
- University, hospital or other
- Collaborators
- Rockefeller University
- Responsible party
- Sponsor-investigator, Darell Bigner, Duke University
- Investigators
- Daniel Landi, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05734560
- Sponsor's protocol ID
- Pro00110119
- Status last verified
- Oct 2026
- First submitted
- 7 Feb 2023
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Delivery of D2C7-IT and 2141-V11 Combination Immunotherapy in Residual Disease for Adult Patients With Newly Diagnosed MGMT Unmethylated Glioblastoma and Perilymphatic Subcutaneous Injections of 2141-V11
- ClinicalTrials.gov ID
- NCT05734560
- Acronym / sponsor ID
- Pro00110119
- Keywords
- D2C7, D2C7-IT, 2141-V11, Pro00110119, GBM, Glioblastoma, convection-enhanced delivery, CED
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Darell BignerUniversity, hospital or other
- Collaborators
- Rockefeller University
- Study start
- 6 Sep 2023 (actual)
- Primary completion
- 31 Oct 2026 (estimated)
- Study completion
- 31 Oct 2028 (estimated)
- First posted
- 21 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to determine the safety and efficacy of administering a single intracerebral (within the brain) dose of investigational compounds called D2C7-immunotoxin (IT) and 2141-V11 in residual disease (within tumor margins) after surgery, followed by later repeated injections of 2141-V11 in the subcutaneous area (under the skin) around the lymph nodes of the head and neck for adults newly diagnosed with a type of cancerous brain tumor called glioblastoma. The word "investigational" means the study drugs are still being tested in research studies and are not approved by the U.S. Food and Drug Administration (FDA).
Detailed description
Within this study, approximately 50 study participants will receive a single infusion of D2C7-IT in the hospital, which is delivered to the tumor margins over 3 days through a catheter placed in the brain, followed by a single infusion of 2141-V11 delivered over 7 hours to the tumor margins through the same catheter. About 2 weeks after intratumoral infusion of D2C7-IT and 2141-V11, participants will have their first subcutaneous (under the skin) injection of 2141-V11 in the area around the lymph nodes of the head and neck on the same side as the tumor. About a week after this injection, participants will start standard radiation therapy (RT), which typically lasts either 3 weeks or 6 weeks depending upon age. Once RT is finished, participants will resume injections in the area around the lymph nodes of the head and neck on the same side as the tumor of 2141-V11 about 1 week later. They will have another injection about 3 weeks after finishing RT and then start a schedule of injections about every 3 weeks for up to a year.
There are risks to the study drugs that are described in this document. Some common risks related to D2C7-IT include: effects related to tumor cells dying (tumor necrosis), effects on normal brain tissue, effects related to catheter placement and removal, effects related to fluid infusion into the brain (intracerebral infusion), and reactions to the D2C7-IT being directly infused in your brain. Risks of 2141-V11 being directly infused in your brain and injected in the area around the lymph nodes of the head and neck could include: cytokine release syndrome (release of immune system cells called cytokines that can cause fever, chills, headache, muscle pain, itching, rash, chest tightness, palpitations, shortness of breath, low blood pressure, nausea, vomiting), swelling and redness in the neck area, overstimulation of your immune system such that it attacks other tissues in your body, elevated liver enzymes, and low platelets in the blood.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| D2C7-IT + 2141-V11 | Experimental | Drug: D2C7-IT, Drug: 2141-V11Single D2C7-IT intratumoral infusion (6920 ng/mL in 36 mL) over 72 hours followed by single 2141-V11 infusion (5 dose levels) over 7 hours followed by an injection of 2141-V11 in the cervical perilymphatic subcutaneous area ipsilateral to the tumor at week 2, radiation, and further injections of 2141-V11 in the cervical perilymphatic subcutaneous area ipsilateral to the tumor. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Age ≥ 18 years of age at the time of entry into the study
- Newly diagnosed supratentorial GBM, WHO grade 4, IDH wildtype, MGMT unmethylated (high grade glioma with molecular features of GBM will be eligible under WHO 4 malignant glioma) with residual radiographic non-contrast enhancing disease on the post-2 cycles of adjuvant TMZ MRI amenable to catheter placement. The residual radiographic contrast enhancing disease is ≤ 3 cm in maximal diameter in any plane.
- Patient must have completed standard of care radiation therapy (typically 59.4-60 Gy over approximately 6 weeks duration if under 65 years old and a minimum of 40 Gy over 3 weeks duration if 65 years or older) in combination with TMZ and 2 cycles of post-radiation, adjuvant TMZ. For patients known to be MGMT promoter unmethylated prior to start of radiation therapy, patients are not mandated to have received TMZ in combination to radiation therapy prior to participating in this trial.
- Karnofsky Performance Score (KPS) > 70%
- Able to undergo brain MRI wiht and without contrast
Key exclusion criteria (19 listed)
- Patients who are pregnant or breast-feeding/chestfeeding
- Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons or their designate
- Patients with severe, active comorbidity, defined as follows:
- Patients who previously received other therapeutic interventions for newly diagnosed GBM with the exception of surgical resection and standard of care concomitant radiation therapy and TMZ and 2 cycles of post-radiation, adjuvant TMZ for their brain tumor
- Patients who have received concomitant radiation therapy and TMZ ≤ 11 weeks prior to start of D2C7-IT CED infusion
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| D2C7-ITD2C7-IT will be dosed at 166,075 ng in 36 mL. | Drug | D2C7-IT + 2141-V11 |
| 2141-V112141-V11 will be dosed at 3 mg in 3.5 mL for CED administration. 2141-V11 in the cervical perilymphatic subcutaneous area will be dosed at 2 mg. | Drug | D2C7-IT + 2141-V11 |
Primary outcome
Median survival defined as the time between initiation of treatment with D2C7-IT in combination with 2141-V11 and death, or last follow up if alive.
Time frame: 3 years
4 secondary outcomes
Safety as measured by the proportion of patients with unacceptable adverse events due to the combination of D2C7-IT and 2141-V11 administered via CED
Time frame: 6 months
Safety as measured by the proportion of patients with unacceptable adverse events due to pre-radiation therapy administration of cervical perilymphatic injections of 2141-V11, or delayed completion of radiation therapy
Time frame: 6 months
Safety as measured by 6-month progression-free survival (PFS6)
Time frame: 6 months
Median PFS will be reported, which is defined as the median time between initiation of D2C7-IT and 2141-V11 infusion treatment and initial failure (disease progression or death).
Time frame: 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- The Preston Robert Tisch Brain Tumor CenterLink provided by the sponsor.
- Duke HealthLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Daniel Landi, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing D2C7-IT and 2141-V11 in people with Newly Diagnosed MGMT Unmethylated Glioblastoma, run by Darell Bigner at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Daniel Landi, MD (919-684-5301, dukebrain1@dm.duke.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median survival defined as the time between initiation of treatment with D2C7-IT in combination with 2141-V11 and death, or last follow up if alive. (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.