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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
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
Secondary ID [1] 0 0
NST-628-001
Universal Trial Number (UTN)
Trial acronym
NST-628
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Oncology 0 0
MEK Mutation 0 0
RAF Gene Mutation 0 0
Ras (KRAS or NRAS) Gene Mutation 0 0
Melanoma 0 0
NSCLC 0 0
Glioma 0 0
Solid Tumor, Adult 0 0
MAPK Pathway Gene Mutation 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A and B: Evaluate the safety of NST-628 in patients with advanced solid tumors
Timepoint [1] 0 0
Through study completion, an average of 1 year
Primary outcome [2] 0 0
Part A: Determine the recommended dose for expansion of NST-628
Timepoint [2] 0 0
The first 28 days of treatment (DLTs)
Primary outcome [3] 0 0
Part B: Evaluate objective tumor response rate
Timepoint [3] 0 0
Through study completion, an average of 1 year
Secondary outcome [1] 0 0
Part A: Evaluate objective tumor response rate
Timepoint [1] 0 0
Through study completion, an average of 1 year
Secondary outcome [2] 0 0
Part A and B: Evaluate progression free survival (PFS)
Timepoint [2] 0 0
Through study completion, an average of 1 year
Secondary outcome [3] 0 0
Part A and B: Evaluate overall survival (OS)
Timepoint [3] 0 0
Through study completion, an average of 2 years
Secondary outcome [4] 0 0
Part A and B: Characterize the pharmacokinetics of NST-628
Timepoint [4] 0 0
Through study completion, an average of 1 year

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/04/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2029
Actual
Sample size
Target
230
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Scientia Clinical Research, Ltd - Rand
Recruitment hospital [2] 0 0
The Kinghorn Cancer Center, St. Vincent's Health Network - Sidney
Recruitment hospital [3] 0 0
Gallipoli Medical Research Centre- Greenslopes Private Hospital - Greenslopes
Recruitment hospital [4] 0 0
One Clinical Research, Pty Ltd - Nedlands
Recruitment hospital [5] 0 0
Southern Oncology Research Unit - Adelaide
Recruitment postcode(s) [1] 0 0
2031 - Rand
Recruitment postcode(s) [2] 0 0
2010 - Sidney
Recruitment postcode(s) [3] 0 0
120 - Greenslopes
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment postcode(s) [5] 0 0
5042 - Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Texas
Country [2] 0 0
United States of America
State/province [2] 0 0
Virginia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Nested Therapeutics, Inc
Address
Country

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06326411
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
CMO
Address 0 0
Country 0 0
Phone 0 0
617-468-4292
Fax 0 0
Email 0 0
info@nestedtx.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06326411