Investigating NST-628 Oral Tablets for Patients with Solid Tumors

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• UCSF Helen Diller Family Comprehensive Cancer Center
  San Francisco, California, United States Recruiting
• UCLA Hematology/Oncology
  Westwood, Los Angeles, California, United States Recruiting
• Sarah Cannon Research Institute at Health ONE
  Denver, Colorado, United States Recruiting
• Moffitt Cancer Center
  Tampa, Florida, United States Recruiting
• Roswell Park
  Buffalo, New York, United States Recruiting
• Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
  New York, New York, United States Recruiting

Study contacts

• Study coordinator: Cmo
• Email: info@nestedtx.com
• Phone: 617-468-4292

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.