Glioma, Recurrent High GradeEarly Phase 1NCT07784985
A Study of NST-628 in Recurrent Grade 4 Glioma
A Early Phase 1 study testing NST-628 in people with Glioma, Recurrent High Grade and Grade 4 Malignant Glioma, run by Nader Sanai at 1 site in United States.
Trial summary
This is an open-label, single arm, non-randomized, Phase 0 and expansion Phase 1 study of NST-628 in adult patients with recurrent Grade 4 glioma with high phosphorylated extracellular signal-regulated kinase (pERK) expression who are scheduled for surgical resection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioma, Recurrent High Grade, Grade 4 Malignant Glioma
- What is being tested?
- NST-628
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2026to Jul 2028
- Phase
- Early Phase 1
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
- 1. Diagnosed with Grade 4 glioma, who have progressed on or following standard of care therapy, including maximal safe resection (biopsy allowed if resection was deemed unsafe) and concurrent chemoradiation.
- 2. Has sufficient archival or biopsy brain tumor tissue available to confirm eligibility, and the tissue must have an H-Score > 150 for pERK.
- 3. Is clinically indicated for tumor resection and has measurable disease (preoperatively), defined as at least one contrast-enhancing lesion with two perpendicular measurements of at least 1 cm.
- 4. Age ≥ 18 at time of consent.
- 5. Has a performance status of ≤ 2 on the ECOG scale.
- 6. Able to swallow oral medications without crushing or chewing.
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- 7. Has adequate bone marrow and organ function as defined by the laboratory values below (as assessed by the local laboratory for eligibility). Participants not meeting one or more of the laboratory criteria below may still be considered eligible at the discretion of the investigator if the abnormality is not deemed clinically significant, is attributable to the underlying disease or concurrent medications, or if the investigator determines that study participation is appropriate based on an assessment of the potential risks and anticipated benefits. The rationale for eligibility outside of the specified laboratory parameters must be documented in the participant's source records.
- 8. For women of childbearing potential: a. Must have a confirmed negative serum pregnancy test (β-hCG) before starting study treatment (within 24 hours of first dose of study treatment); in rare cases where hCG is suspected to be elevated in the absence of pregnancy (e.g., due to a tumor producing hCG), an ultrasound must be performed to rule out possible pregnancy. b. Must use highly effective contraception (with a failure rate of < 1% per year and low user dependency) for at least 28 days prior to study treatment, and agree to use such a method during study participation and for an additional 6 months after final study drug administration. c. Agrees not to breastfeed starting at screening, during study participation, and for an additional 6 months after final study drug administration. d. Agrees not to donate eggs (ova, oocytes) for the purpose of reproduction starting at screening, during study participation, and for an additional 6 months after final study drug administration.
- 9. For women of non-childbearing potential, is no longer of childbearing potential due to surgical, chemical, or natural menopause.
- 10. For men: a. Agrees not to donate sperm starting at screening, during study participation, and for an additional 6 months after final study drug administration. b. Abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agrees to remain abstinent starting at screening, during study participation, and for 6 months after final study drug administration, or; must use a male condom (even if vasectomized) to ensure effective contraception/prevent delivery of the study drug via seminal fluid starting at screening, during study participation, and for an additional 6 months after final study drug administration.
- 11. Agrees to adhere to protocol defined Lifestyle Considerations starting at screening during study participation.
- 12. Able and willing to comply with scheduled visits, treatment plans, laboratory tests, and other procedures.
- 13. Understands the informed consent document and voluntarily agrees to participate by providing written informed consent (personally or via a legally authorized representative, with assent if applicable). Written informed consent must be obtained before any screening procedures. If consent cannot be expressed in writing, consent must be formally documented and witnessed, preferably by an independent, trusted witness.
Who cannot join
- 1. Has extracranial disease, or evidence of leptomeningeal disease.
- 2. Has a history or current evidence of significant retinal pathology associated with an increased risk of RVO, including any of the following: a. History of RVO; b. Visible retinal pathology as assessed by ophthalmic examination, such as: i. Evidence of new optic disc cupping; ii. Evidence of new peripheral visual field defects; iii. Intraocular pressure > 21 mmHg; iv. Evidence of retinal detachment.
- 3. Has a history or evidence of CV risk, including any of the following: a. QT interval corrected for heart rate using the Fridericia's formula, QTcF ≥ 470 msec; b. History or evidence of current, clinically significant, uncontrolled arrhythmias (those that would require a pacemaker and are not normalized by medication: symptomatic A-fib, clinically significant 2nd or 3rd degree heart block, other clinically significant supraventricular arrhythmias, any obvious ventricular arrhythmias); c. History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months prior to Study Day 1; d. NYHA Class II or higher congestive heart failure; e. Treatment-refractory hypertension, defined as systolic blood pressure > 140mmHg and/or diastolic > 90mmHg despite anti-hypertensive therapy; f. Presence of intracardiac defibrillator or pacemaker.
- 4. Has a history or current evidence of pneumonitis or ILD within 6 months of Day 1.
- 5. Has received more than 2 lines of prior systemic therapy.
- 6. Has received chemotherapy, radiation, gene therapy, vaccine therapy, or anti-cancer antibodies/antibody-drug conjugates within 28 days prior to Day 1, or ongoing treatment-related AEs Grade > 1 per NCI-CTCAE v5.0 (excluding alopecia) at the time of starting study treatment. Individuals with chronic Grade 2 unresolved toxicities might be deemed eligible following discussion with the Sponsor-Investigator.
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- 7. Has received prior treatment with another investigational drug or other intervention within 14 days or 5 half-lives of the investigational product (whichever is less) of Day 1, or a longer period if clinically indicated.
- 8. Has undergone a minor surgical procedure ≤ 5 days or major surgical procedure ≤ 21 days, prior to Day 1.
- 9. Has a known infection with HIV, HBV, or HCV; individuals with laboratory evidence of cleared HBV or HCV infection are permitted. Serologic status reflecting active HBV or HCV: HbsAg or hepatitis B PCR positivity. Individuals who are anti-HBc positive and HbsAg negative will need to have a negative HBV PCR result to be eligible; HCV PCR positivity. Subjects who are HCV antibody positive will need to have a negative PCR result to be eligible.
- 10. Has serious and/or uncontrolled preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (e.g., substance abuse, psychiatric disturbance, uncontrolled intercurrent illness).
- 11. Women who are pregnant or breastfeeding.
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
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013
Phase 0 Navigator, 602-406-8605, research@ivybraintumorcenter.org
Kelly Braun, MD
About this study
Official title: A Phase 0/1 Study of NST-628 in Participants With Recurrent Grade 4 Glioma Scheduled for Resection to Evaluate Central Nervous System (CNS) Penetration With Pharmacodynamic (PD) Triggered Expansion Cohort
This is an open-label, single arm, non-randomized, Phase 0 and expansion Phase 1 study of NST-628 in adult patients with recurrent Grade 4 glioma with high phosphorylated extracellular signal-regulated kinase (pERK) expression who are scheduled for surgical resection. This study will evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability, and anti-tumor activity of NST-628.
Read the detailed description
The study includes two components, a Phase 0 design and an expansion Phase 1 design.
Participants in the Phase 0 component will receive multiple doses of NST-628 orally prior to their planned surgical resection. Blood, CSF, and tumor tissue will be collected intraoperatively to assess PK and PD endpoints. Participants whose tumors express a positive PD response in gadolinium non-enhancing tissue will be eligible to enroll into the Phase 1 component.
Participants in the Phase 1 component will receive NST-628 orally every other day in 28-day cycles. Participants will receive NST-628 as long as the drug is tolerated and the investigator believes the participant may be obtaining benefit. Study treatment will continue until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow up, or study termination by the Sponsor.
Disease progression will be monitored through MRI scans per standard of care and will be assessed using RANO 2.0 criteria.
Participants who terminate study treatment will be contacted for survival data collection.
The end of the study is 12 months after the last participant's last visit.
- Being tested
- NST-628
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NST-628Drug
NST-628 is a small molecule non-covalent pan-RAF/MEK dual molecular glue targeting RAF and MEK nodes of MAPK pathway.
| Study group | Role | What they receive |
|---|---|---|
| Recurrent Grade 4 Glioma | Experimental | Participants with high pERK expression in pretreatment biopsy/archival tumor tissue: tumors with an H Score > 150. Receives: Drug: NST-628 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 0: Percent Change of pERK Expression in Tumor Tissue
Percent change of pERK in post-treatment (Phase 0) tumor tissue compared to matched pretreatment (archival) tumor tissue
Measured: Intraoperatively
Phase 1: Incidence of Adverse Events as Assessed by CTCAE v5.0
Incidence of the following will be summarized: AEs and SAEs; treatment discontinuations, dose interruptions, and dose reductions due to AEs; clinically-significant changes in vital signs, body weight, laboratory tests, ECG, and ECOG performance status.
Measured: Date of first dose until 30-days post last dose
Secondary outcomes (12)
Phase 0: Mean Total NST-628 Concentration in Gadolinium Enhancing and Non-enhancing Tumor Tissue
Tumor tissue collected during Phase 0 surgery
Measured: Intraoperatively
Phase 0: Mean Unbound NST-628 Concentration in Gadolinium Enhancing and Non-enhancing Tumor Tissue
Tumor tissue collected during Phase 0 surgery
Measured: Intraoperatively
Phase 0: Median Total NST-628 Concentration in Gadolinium Enhancing and Non-enhancing Tumor Tissue
Tumor tissue collected during Phase 0 surgery
Measured: Intraoperatively
Phase 0: Median Unbound NST-628 Concentration in Gadolinium Enhancing and Non-enhancing Tumor Tissue
Tumor tissue collected during Phase 0 surgery
Measured: Intraoperatively
Phase 0: Mean NST-628 Concentration in CSF
CSF collected during Phase 0 surgery
Measured: Intraoperatively
Phase 0: Median NST-628 Concentration in CSF
CSF collected during Phase 0 surgery
Measured: Intraoperatively
Phase 0: Peak NST-628 Concentration in Plasma (Cmax)
Blood plasma collected prior to dose, during Phase 0 surgery, and post-op
Measured: Prior to dose (trough level), 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose
Phase 0: Time to Peak NST-628 Concentration in Plasma (Tmax)
Blood plasma collected prior to dose, during Phase 0 surgery, and post-op
Measured: Prior to dose (trough level), 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose
Phase 0: NST-628 Half-life in Plasma (t1/2)
Blood plasma collected prior to dose, during Phase 0 surgery, and post-op
Measured: Prior to dose (trough level), 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose
Phase 0: Area Under the Plasma NST-628 Concentration versus Time Curve (AUC)
Blood plasma collected prior to dose, during Phase 0 surgery, and post-op
Measured: Prior to dose (trough level), 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose
Phase 1: Proportion of Participants Alive at 12 Months (OS12)
Overall Survival (OS) will be analyzed using Kaplan-Meier methods. Participants without a death event will be censored at the last known alive date.
Measured: Date of Phase 0 surgery to date of death from any cause, assessed up to 12 months
Phase 1: Proportion of Participants Progression-Free at 6 Months (PFS6) as Assessed by RANO 2.0
Progression-Free Survival at 6 months will be analyzed using Kaplan-Meier methods.
Measured: Date of Phase 0 surgery to date of protocol-defined disease progression, assessed up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2026
- Study startOct 2026 (estimated)
- Primary completionJul 2027 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioma, Recurrent High GradeStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nader Sanai
- Sponsor type
- University, hospital or other
- Collaborators
- Barrow Neurological Institute, Nested Therapeutics, Inc, Dignity Health
- Responsible party
- Sponsor-investigator, Nader Sanai, St. Joseph's Hospital and Medical Center, Phoenix
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07784985
- Sponsor's protocol ID
- 2024-23
- Status last verified
- Aug 2026
- First submitted
- 19 Aug 2026
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No