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

NCT07392957 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202602098
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief 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. 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

Keywords

VEGF; 4-1BB; CD137; glioblastoma; immunotherapy; targeted therapy; CTX-009; CTX-471

Outcome Measures

Primary Outcomes (5)

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

  Adverse events will be graded according to CTCAE v5.0

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

• 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.

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

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

  Adverse events will be graded according to CTCAE v5.0

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

• 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.

  12 months

• 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.

  12 months

Secondary Outcomes (5)

• Overall response rate (ORR)

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

• Duration of response (DoR)

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

• Median progression-free survival (mPFS)

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

• Median overall survival (mOS)

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

• Progression free survival at 9 months (PFS9)

  9 months

Study Arms (4)

Phase IB Arm 1: CTX-009 monotherapy

EXPERIMENTAL

CTX-009 will be given intravenously at the assigned dose level on an outpatient basis every 2 weeks of a 28-day cycle.

Drug: CTX-009

Phase IB Arm 2: CTX-009 and CTX-471 combination therapy

EXPERIMENTAL

CTX-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.

Drug: CTX-009; Drug: CTX-471

Phase II Expansion Arm 1: CTX-009 monotherapy

EXPERIMENTAL

CTX-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.

Drug: CTX-009

Phase II Expansion Arm 2: CTX-009 and CTX-471 combination therapy

EXPERIMENTAL

CTX-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.

Drug: CTX-009; Drug: CTX-471

Interventions

CTX-009 DRUG

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.

Phase IB Arm 1: CTX-009 monotherapy; Phase IB Arm 2: CTX-009 and CTX-471 combination therapy; Phase II Expansion Arm 1: CTX-009 monotherapy; Phase II Expansion Arm 2: CTX-009 and CTX-471 combination therapy

CTX-471 DRUG

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.

Phase IB Arm 2: CTX-009 and CTX-471 combination therapy; Phase II Expansion Arm 2: CTX-009 and CTX-471 combination therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• 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
• 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.

You may not qualify if:

• 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).
• 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
• 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

Sponsors & Collaborators

• Compass Therapeutics: collaborator
• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Tanner M Johanns, MD, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tanner M Johanns, MD, PhD

CONTACT

314-362-9355; tannerjohanns@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: After completion of enrollment to Arm 1 (phase IB and phase II), enrollment will open to Arm 2.

Study Record Dates

• First Submitted: January 29, 2026
• First Posted: February 6, 2026
• Study Start: April 30, 2026
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): April 30, 2031
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 36 months following article publication
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.

Locations

US (1)