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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT06326411
Registration number
NCT06326411
Ethics application status
Date submitted
15/03/2024
Date registered
22/03/2024
Date last updated
31/05/2024
Titles & IDs
Public title
A Study to Investigate the Safety and Efficacy of NST-628 Oral Tablets in Subjects With Solid Tumors
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Scientific title
A Phase I, Open Label Single-arm Two-part Study to Investigate Safety, Pharmacokinetics, and Preliminary Efficacy of Pan-RAF/MEK Glue NST-628 Oral Tablets in Subject With Solid Tumors Harboring Genetic Alterations in the MAPK Pathway and With Other Solid Tumors
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Secondary ID [1]
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NST-628-001
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Universal Trial Number (UTN)
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Trial acronym
NST-628
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Oncology
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MEK Mutation
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RAF Gene Mutation
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Ras (KRAS or NRAS) Gene Mutation
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Melanoma
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NSCLC
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Glioma
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Solid Tumor, Adult
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MAPK Pathway Gene Mutation
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Condition category
Condition code
Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - NST-628
Experimental: Part A Dose Escalation and Part B Dose Expansion - Part A will evaluate the safety of NST-628 with advanced solid tumors and determine the recommended dose for expansion of NST-628.
Part B will evaluate the objective tumor response rate in subjects with advanced solid tumors harboring specified genetic alterations receiving NST-628 and evaluate the safety of NST-628 in subjects with advanced solid tumors in cohorts defined below:
i. Melanoma Cohorts
Activating NRAS mutations
Select BRAF alterations
ii. Non-Melanoma Cohorts:
Solid tumors with NRAS activating mutations
Solid tumors with KRAS activating mutations
Solid tumors with select BRAF alterations
Glioma with BRAF alterations
Treatment: Drugs: NST-628
NST-628 is a small molecule non-covalent pan-RAF/MEK dual molecular glue targeting RAF and MEK nodes of MAPK pathway.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Part A and B: Evaluate the safety of NST-628 in patients with advanced solid tumors
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Assessment method [1]
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Adverse effects
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Timepoint [1]
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Through study completion, an average of 1 year
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Primary outcome [2]
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Part A: Determine the recommended dose for expansion of NST-628
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Assessment method [2]
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Dose limiting toxicities (DLTs)
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Timepoint [2]
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The first 28 days of treatment (DLTs)
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Primary outcome [3]
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Part B: Evaluate objective tumor response rate
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Assessment method [3]
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Objective response per RECIST v. 1.1 or other response assessment tool standard for a given tumor type.
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Timepoint [3]
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Through study completion, an average of 1 year
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Secondary outcome [1]
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Part A: Evaluate objective tumor response rate
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Assessment method [1]
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Objective response per RECIST v. 1.1 or other response assessment tool standard for a given tumor type.
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Timepoint [1]
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Through study completion, an average of 1 year
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Secondary outcome [2]
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Part A and B: Evaluate progression free survival (PFS)
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Assessment method [2]
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PFS defined as the time to first occurrence of disease progression per RECIST v1.1 (or other response assessment tool standard for a given tumor type) or death
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Timepoint [2]
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Through study completion, an average of 1 year
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Secondary outcome [3]
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Part A and B: Evaluate overall survival (OS)
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Assessment method [3]
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Overall survival (OS) defined as the time to death
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Timepoint [3]
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Through study completion, an average of 2 years
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Secondary outcome [4]
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Part A and B: Characterize the pharmacokinetics of NST-628
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Assessment method [4]
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NST-628 concentrations in plasma
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Timepoint [4]
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Through study completion, an average of 1 year
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Eligibility
Key inclusion criteria
Subjects are eligible to be included in the study only if all of the following criteria
apply:
1. Subjects must be =18 years old (or of legal age of consent in the country in which the
study is taking place) at the time of signing the informed consent.
2. Subjects who have a histologically or cytologically documented metastatic or locally
advanced solid tumor, for which standard of care (SoC) therapy does not exist, no
longer provides benefit, or is not tolerated by the subject, or the subject has been
assessed by the Investigator as not being suitable for SoC therapy.
1. Part A: Subjects with any solid tumor with genetic alteration of or evidence of
tumor dependence upon the RAS/MAPK pathway (subject to additional restrictions
specified in the study protocol)
2. Part B: Subjects must be diagnosed with one of the following solid tumors
harboring specified genetic alterations based on a validated local test:
i. Melanoma Cohorts:
1. Activating NRAS mutations
2. Select BRAF alterations
ii. Non-Melanoma Cohorts:
1. Solid tumors with NRAS activating mutations
2. Solid tumors with KRAS activating mutations
3. Solid tumors with select BRAF alterations
4. Glioma with BRAF alterations
3. Newly obtained or archived tumor tissue is required
4. Part B: measurable disease as defined by RECIST Version 1.1 or by other disease
assessment tool standard for a given tumor type (if RECIST v. 1.1 is not standard)
5. Performance status
1. Solid tumors other than glioma: ECOG 0 or 1
2. Glioma: Karnofsky = 70 and ECOG 0 or 1
6. Have adequate organ function
7. Understand and voluntarily sign an Institutional Review Board/Independent Ethics
Committee-approved informed consent form prior to any study-specific evaluation.
8. Life expectancy = 12 weeks
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
Subjects are excluded from the study if any of the following criteria apply:
1. Conditions interfering with oral intake of NST-628
2. Conditions interfering with intestinal absorption of an orally administered drug
3. A history or current evidence of significant retinal pathology leading to increased
risk of RVO
4. A history or evidence of cardiovascular risk
5. Current or history within 6 months of planned Cycle 1 Day 1 of pneumonitis or
interstitial lung disease (ILD)
6. Part B: prior treatment with any MEK or BRAF inhibitor
7. Untreated or symptomatic central nervous system (CNS) metastases
8. Chemotherapy, radiation, gene therapy, vaccine therapy, or anti-cancer antibodies /
ADCs within 28 days of Cycle 1 Day 1
9. Targeted small molecule agents within 14 days or 5 half-lives of Cycle 1 Day 1
10. Females who are pregnant or breastfeeding.
11. For fertile patients (female able to become pregnant or male able to father a child),
refusal to use effective contraception during the period of the trial and for 6 months
after the last dose of NST-628
12. Presence of any serious or unstable concomitant systemic disorder incompatible with
the clinical study
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Study design
Purpose of the study
Treatment
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Other
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
9/04/2024
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
1/11/2029
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Actual
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Sample size
Target
230
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
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Recruitment hospital [1]
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Scientia Clinical Research, Ltd - Rand
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Recruitment hospital [2]
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The Kinghorn Cancer Center, St. Vincent's Health Network - Sidney
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Recruitment hospital [3]
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Gallipoli Medical Research Centre- Greenslopes Private Hospital - Greenslopes
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Recruitment hospital [4]
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One Clinical Research, Pty Ltd - Nedlands
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Recruitment hospital [5]
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Southern Oncology Research Unit - Adelaide
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Recruitment postcode(s) [1]
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2031 - Rand
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Recruitment postcode(s) [2]
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2010 - Sidney
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Recruitment postcode(s) [3]
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120 - Greenslopes
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Recruitment postcode(s) [4]
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6009 - Nedlands
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Recruitment postcode(s) [5]
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5042 - Adelaide
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Texas
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Country [2]
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United States of America
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State/province [2]
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Virginia
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Nested Therapeutics, Inc
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
This is a two-part Phase 1, open label, multi-center, single arm, non-randomized, multiple
dose, safety, pharmacokinetic (PK) and preliminary efficacy study of single agent NST-628 in
adult patients with MAPK pathway mutated/dependent advanced solid tumors who have exhausted
standard treatment options.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT06326411
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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CMO
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Address
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Country
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Phone
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617-468-4292
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT06326411
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