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GlioblastomaPhase 1/2NCT07392957

Safety and Efficacy of CTX-009 With or Without CTX-471 for Recurrent Glioblastoma

A Phase 1/2 study testing CTX-009 and CTX-471 in people with Glioblastoma, run by Washington University School of Medicine at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a phase IB/II, open-label study evaluating CTX-009 as monotherapy and in combination with CTX-471. The study evaluates the safety and efficacy of the monotherapy and the combination in patients with recurrent glioblastoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma
What is being tested?
CTX-009 and CTX-471
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
1 siteUnited States
Study dates
16 Jun 2026to 30 Jun 2031
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

  • Histologically or radiographically confirmed recurrent CNS WHO grade 4 IDH wild-type glioma following standard of care treatment including radiation, chemotherapy, and/or tumor-treating fields. No more than 2 recurrences are allowed.
  • Patients may receive palliative treatment for recurrent disease prior to study enrollment with surgery or laser thermal ablation but must wait at least 4 weeks post-procedure to start study drug(s) and must have recovered from all procedure-related complications.
  • At least 18 years of age.
  • KPS performance status ≥ 60%
  • Adequate bone marrow and organ function as defined below:
  • Absolute neutrophil count ≥ 1.0 K/cumm
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  • Platelets ≥ 75 K/cumm
  • Hemoglobin ≥ 8.0 g/dL
  • Total bilirubin ≤ 1.5 x IULN, unless suspected or documented history of Gilbert's Syndrome, in which case ≤ 2.5 x IULN
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
  • Creatinine clearance > 30 mL/min by Cockcroft-Gault
  • Urine Protein : Creatinine ratio (UPCR) < 300 mg/g
  • QTcF < 480 msec; in the setting of bundle branch block or other arrhythmia that makes QTcF unreliable, a JT interval < 350 msec can be used as a substitute.
  • The effects of CTX-009 and CTX-471 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 4 months after completion of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.
  • Resolution, or stable control with medical management, of all prior anti-cancer therapy toxicities to ≤ grade 1 per NCI-CTCAE v5.0. If the patient has had major surgery, 4 weeks must have elapsed from the date of surgery and the first dose of study drug(s).
  • Stable or decreasing dose of corticosteroids and anti-seizure medications for 7 days prior to start of study drug(s). For Arm 2: a maximum of 2 mg daily dose of dexamethasone or equivalent at time of study drug(s) initiation is allowed.
  • Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Who cannot join

  • Have progressed on prior anti-VEGF-A therapy (i.e., bevacizumab) or developed clinically significant adverse reaction to any anti-VEGF therapy (i.e., bevacizumab, regorafenib) which led to discontinuation of treatment. Prior treatment with low dose anti-VEGF therapy for management of symptomatic vasogenic edema or radiation necrosis is permitted as long as progression was not noted while receiving treatment with the anti-VEGF agent, and is not needed for continued control of symptoms. A 4-week washout from last dose of low-dose anti-VEGF therapy is required.
  • Prior systemic anti-cancer therapy including: investigational agents or immunotherapy within 4 weeks (can consider 2 week interval for agents with known 5 half-lives <14 days following discussion with study PI); chemotherapy within 4 weeks (6 weeks for BCNU or CCNU); or targeted therapy within 2 weeks prior to treatment.
  • Note: participants must have recovered from all clinically significant AEs due to previous therapies to ≤ grade 1 or baseline. This does not include AEs deemed not clinically significant by treating physician (i.e., alopecia). Participants with endocrine-related AEs ≤ grade 2 requiring treatment or hormone replacement are eligible if controlled (i.e., clinically asymptomatic) on stable dose of replacement therapy.
  • Use of aspirin, NSAIDs, or other antiplatelet agents within 7 days of study drug(s) initiation. Regular use (i.e., daily) of these agents should be avoided while on study treatment.
  • Use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes within 7 days of study drug(s) initiation. Prophylactic dosing of DOAC, such as apixaban or edoxaban, or LMWH for patency of venous access devices is allowed (preference is given to DOAC over LMWH).
  • History of intraparenchymal or subdural hemorrhage. History of hemorrhage-related or gastroenterological disease including active hemorrhage, hemorrhagic diathesis, coagulopathy, or tumor in great arteries. History of clinically significant gastroenterological disease, such as peptic ulcer, GI bleeding, GI or non-GI fistula, perforation, abdominal abscess, percutaneous drains, clinical symptoms and signs of GI obstruction, need for parenteral hydration or nutrition, or inflammatory bowel disease (IBD).
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  • History of unprovoked high-risk thromboembolic events.
  • A history of the following cardiovascular diseases in the past 5 years (a case-by-case evaluation can be considered in consultation with the study PI):
  • Congestive heart failure that corresponds to Class II or a higher class under NYHA classification or < 50% of LVEF
  • Uncontrolled hypertension (140/90 mmHg despite best care including anti-hypertensive medications). White coat hypertension is not exclusionary.
  • Hypertensive crisis or pre-existing hypertensive encephalopathy
  • Pulmonary hypertension
  • Myocardial infarction
  • Uncontrolled arrhythmia
  • Unstable angina
  • Significant vascular diseases (e.g., aortic aneurysm requiring surgery or recent peripheral artery thrombosis) within 6 months prior to study entry
  • For Arm 2: Prior treatment with other investigational immune-oncology therapies targeting CD137 (4-1BB).
  • For Arm 2: Systemic therapy with non-steroidal immunosuppressive agents within 7 days prior to first dose. Patients with a prior history of autoimmune disease not requiring immunosuppressive therapy may be eligible following discussion with the study PI. Topical, intranasal, intraocular, or inhaled corticosteroids and physiologic replacement for patients with adrenal insufficiency are allowed.
  • Prior solid organ or hematologic cell transplantation.
  • For Arm 2: Has received a live or live-attenuated vaccine within 30 days prior to the first dose. Note: administration of killed vaccines is allowed.
  • Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to CTX-009 or CTX-471.
  • Active uncontrolled seizure disorder.
  • Active uncontrolled intercurrent illness including, but not limited to: infection, hypertension, open wound(s), or cardiac arrhythmia. Chronic illnesses controlled (i.e., clinically asymptomatic) with oral medications are allowed.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 7 days of first dose for Arm 1 or 72 hours of first dose for Arm 2.
  • HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.
  • Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.
  • History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Tanner M Johanns, MD, PhD contact

314-362-9355

tannerjohanns@wustl.edu

United States1 site, 1 recruiting

  • Washington University School of Medicine

    St Louis, Missouri, 63110

    Tanner M Johanns, MD, PhD, 314-362-9355, tannerjohanns@wustl.edu

    Tanner M Johanns, MD, PhD

    Recruiting

Other trials in United States

About this study

Official title: A Phase IB/II Open-label Study of the Safety and Preliminary Efficacy of CTX-009 Administered Either as a Monotherapy or in Combination With CTX-471 in Patients With Recurrent Glioblastoma

This is a phase IB/II, open-label study evaluating CTX-009 as monotherapy and in combination with CTX-471. The study evaluates the safety and efficacy of the monotherapy and the combination in patients with recurrent glioblastoma. The study tests the hypothesis that treatment with CTX-009 alone or in combination with CTX-471 will lead to enhanced tumor control and prolongation of overall survival of patients with recurrent glioblastoma.

CTX-009 expands on existing anti-angiogenic therapies by ablating key compensatory and resistance mechanisms to bevacizumab, CTX-471 restores local immune reactivity through activation of costimulatory immune mediators. Combination of these two agents may further impair tumor proliferation through synergistic effects on the tumor microenvironment

Conditions
Glioblastoma
Being tested
CTX-009, CTX-471
Keywords
VEGF, 4-1BB, CD137, glioblastoma, immunotherapy, targeted therapy, CTX-009, CTX-471
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CTX-009Drug

    Also called Tovecimig

    CTX-009 will be given intravenously over the course of 60 minutes (+/- 5 minutes) on an outpatient basis every 2 weeks of a 28-day cycle.

  • CTX-471Drug

    CTX-471 will be given intravenously over the course of 30 minutes (-5/+10) on an outpatient basis every 2 weeks of a 28-day cycle.

Study groups in NCT07392957
Study groupRoleWhat they receive
Phase IB Arm 1: CTX-009 monotherapyExperimentalCTX-009 will be given intravenously at the assigned dose level on an outpatient basis every 2 weeks of a 28-day cycle.
Receives: Drug: CTX-009
Phase IB Arm 2: CTX-009 and CTX-471 combination therapyExperimentalCTX-009 will be given intravenously at the dose determined to be the recommended phase II dose (RP2D) in Arm 1 every 2 weeks, and CTX-471 will be given intravenously at a dose of 0.3 mg/kg every 2 weeks (day 1 and day 15). On days when both drugs are given, CTX-009 will be given first, followed by a 30-minute observation period, followed by CTX-471. Cycles will be 28 days.
Receives: Drug: CTX-009; Drug: CTX-471
Phase II Expansion Arm 1: CTX-009 monotherapyExperimentalCTX-009 will be given intravenously at the recommended phase 2 dose (RP2D) determined from Phase IB on an outpatient basis every 2 weeks of a 28-day cycle.
Receives: Drug: CTX-009
Phase II Expansion Arm 2: CTX-009 and CTX-471 combination therapyExperimentalCTX-009 will be given intravenously at the dose determined to be the recommended phase II dose (RP2D) every 2 weeks (day 1 and day 15). CTX-471 will be given intravenously at a dose of 0.3 mg/kg every 2 weeks (day 1 and day 15). On days when both drugs are given, CTX-009 will be given first, followed by a 30-minute observation period, followed by CTX-471. Cycles will be 28 days.
Receives: Drug: CTX-009; Drug: CTX-471

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase IB Arm 1: Toxicity as measured by number of participants with adverse events

    Adverse events will be graded according to CTCAE v6.0

    Measured: Start of treatment through 60 days after treatment (estimated to be 14 months)

  2. Phase IB Arm 1: Recommended Phase 2 Dose (RP2D)

    RP2D will be determined from the phase IB portion of Arm 1 by assessing tolerability. Tolerability is defined as ≤1 among patients experiencing excessive dose limiting toxicities (DLTs). The dose level in phase IB determined to be tolerable is the RP2D.

    Measured: Start of treatment through completion of cycle 1 (each cycle is 28 days)

  3. Phase IB Arm 2: Toxicity as measured by number of participants with adverse events

    Adverse events will be graded according to CTCAE v6.0

    Measured: Start of treatment through 60 days after treatment (estimated to be 14 months)

  4. Phase II Arm 1: Overall survival rate at 12 months (OS12)

    Overall survival is defined from time of treatment start to time of death due to any cause or latest follow-up, whichever is earlier, with an inference focus on 12-month overall survival.

    Measured: 12 months

  5. Phase II Arm 2: Overall survival rate at 12 months (OS12)

    Overall survival is defined from time of treatment start to time of death due to any cause or latest follow-up, whichever is earlier, with an inference focus on 12-month overall survival.

    Measured: 12 months

Secondary outcomes (5)

  1. Overall response rate (ORR)

    Overall Response Rate (ORR) is measured as the proportion of patients with complete response (CR) or partial response (PR) as defined by the RANO Response criteria.

    CR is defined as disappearance of all enhancing measurable and non-measurable disease for at least 4 weeks, no new lesions, stable or improved non-enhancing (T2/FLAIR) lesions, off corticosteroids and stable or improved clinically. PR is defined as ≥ 50% decrease of all measurable enhancing lesions for at least 4 weeks, no progression of non-measurable disease, stable or improved non-enhancing (T2/FLAIR) lesions, corticosteroid dose no greater than dose at time of baseline scan, stable or improved clinically

    Measured: Start of treatment to end of treatment (estimated total time to be 12 months)

  2. Duration of response (DoR)

    DoR is defined as time from Day 1 of study treatment (CTX-009 with our without CTX-471) to disease progression or death in patients who achieve a complete response (CR) or partial response (PR) as defined by the RANO criteria.

    CR is defined as disappearance of all enhancing measurable and non-measurable disease for at least 4 weeks, no new lesions, stable or improved non-enhancing (T2/FLAIR) lesions, off corticosteroids and stable or improved clinically. PR is defined as ≥ 50% decrease of all measurable enhancing lesions for at least 4 weeks, no progression of non-measurable disease, stable or improved non-enhancing (T2/FLAIR) lesions, corticosteroid dose no greater than dose at time of baseline scan, stable or improved clinically.

    .

    Measured: Start of treatment to disease progression/recurrence (estimated total time to be 36 months)

  3. Median progression-free survival (mPFS)

    mPFS is defined as the time of treatment start to the event of disease progression. Disease progression is measured based on the RANO criteria.

    Measured: Start of treatment to disease progression (estimated to be 36 months)

  4. Median overall survival (mOS)

    mOS is measured as the amount of time from treatment start to death due to any cause or latest follow up, whichever is earlier.

    Measured: Start of treatment through completion of follow up or death (estimated to be 36 months)

  5. Progression free survival at 9 months (PFS9)

    PFS9 is measured as amount of time from the start of treatment to the event of disease progression. Disease progression is measured based on the RANO criteria.

    Measured: 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Feb 2026
  2. Study start16 Jun 2026
  3. Primary completion30 Jun 2029 (estimated)
  4. Study completion30 Jun 2031 (estimated)

Resources

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
Randomised
Intervention model
Sequential
Model description
After completion of enrollment to Arm 1 (phase IB and phase II), enrollment will open to Arm 2.
Masking
None (open label)
Enrolment
54 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07392957
Sponsor's protocol ID
202602098
Status last verified
Jun 2026
First submitted
29 Jan 2026
Last updated
22 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Deidentified individual participant data will be shared that underlie the results reported (text, tables, figures, and appendices).

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CTX-009 and CTX-471 in people with Glioblastoma, run by Washington University School of Medicine 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 17 inclusion and 28 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 22 Jun 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 Tanner M Johanns, MD, PhD (314-362-9355, tannerjohanns@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase IB Arm 1: Toxicity as measured by number of participants with adverse events (time frame: Start of treatment through 60 days after treatment (estimated to be 14 months)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07392957.

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 22 Jun 2026.

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