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Investigating NST-628 Oral Tablets for Patients with Solid Tumors

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

PHASE1 · Nested Therapeutics, Inc · NCT06326411

This study is testing a new oral medication called NST-628 to see if it can safely help adults with advanced solid tumors that have specific genetic mutations.

Quick facts

PhasePHASE1
Study typeInterventional
Enrollment230 (estimated)
Ages18 Years and up
SexAll
SponsorNested Therapeutics, Inc (industry)
Drugs / interventionsChemotherapy, radiation
Locations23 sites (San Francisco, California and 22 other locations)
Trial IDNCT06326411 on ClinicalTrials.gov

What this trial studies

This Phase 1 clinical trial is designed to evaluate the safety and efficacy of NST-628, an oral medication, in adult patients with advanced solid tumors that have mutations in the MAPK pathway. The study consists of two parts: the first part focuses on determining the maximum tolerated dose (MTD) through a dose escalation approach, while the second part aims to assess the treatment's effectiveness at the recommended dose in specific cohorts of patients. Participants will receive NST-628 daily in 28-day cycles, and the study will gather data on safety, pharmacokinetics, and preliminary efficacy. The trial is open-label and non-randomized, allowing for a comprehensive assessment of the drug's impact on patients who have exhausted standard treatment options.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with advanced solid tumors that have specific mutations in the RAS/MAPK pathway and have not benefited from standard treatments.

Not a fit: Patients with solid tumors that do not have the specified genetic alterations or those who are suitable for standard of care therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that currently have no effective standard therapies.

How similar studies have performed: Other studies targeting the MAPK pathway have shown promise, suggesting that this approach may be beneficial, although this specific trial is novel in its focus on NST-628.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

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

Where this trial is running

San Francisco, California and 22 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Oncology, MEK Mutation, RAF Gene Mutation, Ras Gene Mutation, Melanoma, NSCLC, Glioma, Solid Tumor, Adult

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.