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A Study of NST-628 in Recurrent Grade 4 Glioma

ConditionsGlioma, Recurrent High GradeGrade 4 Malignant Glioma
Trial statusNot yet recruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorNader Sanai

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

  • NST-628

    Drug

    NST-628 is a small molecule non-covalent pan-RAF/MEK dual molecular glue targeting RAF and MEK nodes of MAPK pathway.

Treatment groups

12 Participants
are divided into 1 treatment group
Group A: Recurrent Grade 4 GliomaExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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

Time frame
Intraoperatively
2

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.

Time frame
Date of first dose until 30-days post last dose

Secondary outcomes

1

Phase 0: Mean Total NST-628 Concentration in Gadolinium Enhancing and Non-enhancing Tumor Tissue

Tumor tissue collected during Phase 0 surgery

Time frame
Intraoperatively
2

Phase 0: Mean Unbound NST-628 Concentration in Gadolinium Enhancing and Non-enhancing Tumor Tissue

Tumor tissue collected during Phase 0 surgery

Time frame
Intraoperatively
3

Phase 0: Median Total NST-628 Concentration in Gadolinium Enhancing and Non-enhancing Tumor Tissue

Tumor tissue collected during Phase 0 surgery

Time frame
Intraoperatively
4

Phase 0: Median Unbound NST-628 Concentration in Gadolinium Enhancing and Non-enhancing Tumor Tissue

Tumor tissue collected during Phase 0 surgery

Time frame
Intraoperatively

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Nader Sanai

Lead sponsor

St. Joseph's Hospital and Medical Center, Phoenix

Sponsor institution

Barrow Neurological Institute

Collaborator

Nested Therapeutics, Inc

Collaborator

Dignity Health

Collaborator

Source ClinicalTrials.gov

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