A Study to Investigate the Safety and Efficacy of NST-628 Oral Tablets in Subjects With Solid Tumors
NCT ID: NCT06326411
Last Updated: 2025-11-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE1
230 participants
INTERVENTIONAL
2024-04-09
2029-11-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Bayesian Optimal Interval (BOIN) method will be used for dose escalation.
Once MTD is reached or dose escalation is stopped prior to reaching MTD and provisional RDE selected, the provisional RDE level will be expanded. If warranted by dose/toxicity/anti-tumor activity observations, additional, lower dose level(s) may also be expanded.
Part B of the study will include up to 6 cohorts of approximately up to 30 subjects each with select MAPK pathway mutant solid tumors enrolled at the RDE in order to explore benefit from treatment as suggested by preclinical findings and will better define the safety profile of NST-628 at the RDE. Additional safety information gathered in Part B may be used to modify the dose recommended for future studies.
The end of the study is the last visit of the last subject.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SEQUENTIAL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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
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
NST-628
NST-628 is a small molecule non-covalent pan-RAF/MEK dual molecular glue targeting RAF and MEK nodes of MAPK pathway.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
NST-628
NST-628 is a small molecule non-covalent pan-RAF/MEK dual molecular glue targeting RAF and MEK nodes of MAPK pathway.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
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
Exclusion Criteria
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
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Nested Therapeutics, Inc
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
UCLA Hematology/Oncology
Westwood, Los Angeles, California, United States
Sarah Cannon Research Institute at Health ONE
Denver, Colorado, United States
Yale Cancer Center
New Haven, Connecticut, United States
Moffitt Cancer Center
Tampa, Florida, United States
Roswell Park
Buffalo, New York, United States
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, United States
Columbia University Medical Center
New York, New York, United States
Memorial Slone Kettering Cancer Center
New York, New York, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
SCRI Oncology Partners
Nashville, Tennessee, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States
NEXT Oncology - Austin
Austin, Texas, United States
NEXT Oncology - Dallas
Dallas, Texas, United States
MD Anderson Cancer Center
Houston, Texas, United States
START Moutain Region
West Valley City, Utah, United States
NEXT Oncology - Virginia
Fairfax, Virginia, United States
The Kinghorn Cancer Center, St. Vincent's Health Network
Darlinghurst, New South Wales, Australia
Scientia Clinical Research, Ltd
Randwick, New South Wales, Australia
Gallipoli Medical Research Centre- Greenslopes Private Hospital
Greenslopes, Queensland, Australia
Southern Oncology Research Unit
Adelaide, South Australia, Australia
Cabrini Health Limited
Malvern, Victoria, Australia
Cabrini Hospital
Malvern, Victoria, Australia
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Phu Lam Clinical Research Manager
Role: primary
Bartosz Chmielowski, MD
Role: primary
Role: primary
Ingrid Palma
Role: primary
Justin Martin
Role: primary
Role: backup
Study Coordinator
Role: primary
Nurse Navigation Team
Role: primary
Role: primary
Role: primary
Angie Boeing
Role: primary
Brianna Flores
Role: primary
Erica Torres
Role: primary
Rabia Khan
Role: primary
Marie Asay
Role: primary
Blake Patterson
Role: primary
Jia (Jenny) Liu, MD
Role: primary
Shiena Lemin
Role: primary
Sarah McLennan
Role: primary
Meggan O'Riley
Role: primary
Study Coordinator
Role: primary
Study Coordinator
Role: primary
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NST-628-001
Identifier Type: -
Identifier Source: org_study_id