A Study to Investigate the Safety and Efficacy of NST-628 Oral Tablets in Subjects With Solid Tumors

Recruiting now · Phase 1

Conditions studied: Oncology, MEK Mutation, RAF Gene Mutation, Ras (KRAS or NRAS) Gene Mutation, Melanoma, NSCLC, Glioma, Solid Tumor, Adult, MAPK Pathway Gene Mutation

In brief

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.

Key facts

Study ID

NCT06326411

Run by

Nested Therapeutics, Inc

People needed

230

Starts

2024-04-09

Expected to finish

2029-11-01

Last updated by the study team

2026-04-20

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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

You may not qualify if…

• 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 it is running

• Cabrini Hospital — Malvern, Victoria, Australia (enrolling)
• UCLA Hematology/Oncology — Westwood, Los Angeles, California, United States (enrolling)
• Sarah Cannon Research Institute at Health ONE — Denver, Colorado, United States (enrolling)
• The Kinghorn Cancer Center, St. Vincent's Health Network — Darlinghurst, New South Wales, Australia (enrolling)
• Gallipoli Medical Research Centre- Greenslopes Private Hospital — Greenslopes, Queensland, Australia (enrolling)
• Southern Oncology Research Unit — Adelaide, South Australia, Australia (enrolling)
• Cabrini Health Limited — Malvern, Victoria, Australia (enrolling)
• UCSF Helen Diller Family Comprehensive Cancer Center — San Francisco, California, United States (enrolling)
• Moffitt Cancer Center — Tampa, Florida, United States (enrolling)
• Roswell Park — Buffalo, New York, United States (enrolling)
• Laura & Isaac Perlmutter Cancer Center at NYU Langone Health — New York, New York, United States (enrolling)
• Columbia University Medical Center — New York, New York, United States (enrolling)
• Memorial Slone Kettering Cancer Center — New York, New York, United States (enrolling)
• UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (enrolling)
• SCRI Oncology Partners — Nashville, Tennessee, United States (enrolling)
• Vanderbilt-Ingram Cancer Center — Nashville, Tennessee, United States (enrolling)
• MD Anderson Cancer Center — Houston, Texas, United States (enrolling)
• NEXT Oncology - Virginia — Fairfax, Virginia, United States (enrolling)
• Yale Cancer Center — New Haven, Connecticut, United States
• NEXT Oncology - Austin — Austin, Texas, United States
• NEXT Oncology - Dallas — Dallas, Texas, United States
• Scientia Clinical Research, Ltd — Randwick, New South Wales, Australia
• START Moutain Region — West Valley City, Utah, United States

Full record on ClinicalTrials.gov

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