NCT06326411 · Nested Therapeutics, Inc
A Study to Investigate the Safety and Efficacy of NST-628 Oral Tablets in Subjects With Solid Tumors
(NST-628)
What this study is about
This is a two-part Phase 1, open label, multi-center, single treatment group$1, non-randomly assigned, multiple dose, safety, how the drug moves through the body (PK) and preliminary effectiveness study of single agent NST-628 in adult patients with MAPK pathway mutated/dependent advanced solid tumors who have exhausted standard treatment options.
View original scientific description
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Subjects are eligible to be included in the study only if all of the following criteria apply:
- 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.
- 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.
- 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)
- 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:
- 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
- Newly obtained or archived tumor tissue is required
- 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)
- Performance status
- Solid tumors other than glioma: ECOG 0 or 1
- Glioma: Karnofsky ≥ 70 and ECOG 0 or 1
- Have adequate organ function
- Understand and voluntarily sign an Institutional Review Board/Independent Ethics Committee-approved informed consent form prior to any study-specific evaluation.
- Life expectancy ≥ 12 weeks
Exclusion criteria
- Subjects are excluded from the study if any of the following criteria apply:
- Conditions interfering with oral intake of NST-628
- Conditions interfering with intestinal absorption of an orally administered drug
- A history or current evidence of significant retinal pathology leading to increased risk of RVO
- A history or evidence of cardiovascular risk
- Current or history within 6 months of planned Cycle 1 Day 1 of pneumonitis or interstitial lung disease (ILD)
- Part B: prior treatment with any MEK or BRAF inhibitor
- Untreated or symptomatic central nervous system (CNS) metastases
- Chemotherapy, radiation, gene therapy, vaccine therapy, or anti-cancer antibodies / ADCs within 28 days of Cycle 1 Day 1
- Targeted small molecule agents within 14 days or 5 half-lives of Cycle 1 Day 1
- Females who are pregnant or breastfeeding.
- 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
- Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study
Where
- San Francisco, California
- Westwood, Los Angeles, California
- Denver, Colorado
- New Haven, Connecticut
- Tampa, Florida
- Buffalo, New York
- New York, New York
- Pittsburgh, Pennsylvania
- Nashville, Tennessee
- Austin, Texas
- Dallas, Texas
- Houston, Texas
And 2 more locations — see the full list below.
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Apr 20, 2026 · Source of record for eligibility and locations