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

NCT06326411 | Recruiting Phase 1 FDA Drug

• 1 other identifier: NST-628-001
• Study Type: interventional
• Target: 230
• Locations: 2 countries
• Sites: 23

Brief Summary

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.

Conditions

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

Keywords

RAS; MEK; RAF; solid tumor

Outcome Measures

Primary Outcomes (3)

• Part A and B: Evaluate the safety of NST-628 in patients with advanced solid tumors

  Adverse effects

  Through study completion, an average of 1 year

• Part A: Determine the recommended dose for expansion of NST-628

  Dose limiting toxicities (DLTs)

  The first 28 days of treatment (DLTs)

• Part B: Evaluate objective tumor response rate

  Objective response per RECIST v. 1.1 or other response assessment tool standard for a given tumor type.

  Through study completion, an average of 1 year

Secondary Outcomes (4)

• Part A: Evaluate objective tumor response rate

  Through study completion, an average of 1 year

• Part A and B: Evaluate progression free survival (PFS)

  Through study completion, an average of 1 year

• Part A and B: Evaluate overall survival (OS)

  Through study completion, an average of 2 years

• Part A and B: Characterize the pharmacokinetics of NST-628

  Through study completion, an average of 1 year

Study Arms (1)

Part A Dose Escalation and Part B Dose Expansion

EXPERIMENTAL

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

Drug: NST-628

Interventions

NST-628 DRUG

NST-628 is a small molecule non-covalent pan-RAF/MEK dual molecular glue targeting RAF and MEK nodes of MAPK pathway.

Part A Dose Escalation and Part B Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

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

Sponsors & Collaborators

• Nested Therapeutics, Inc: lead

Study Sites (23)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

RECRUITING

UCLA Hematology/Oncology

Westwood, Los Angeles, California, 90024, United States

RECRUITING

Sarah Cannon Research Institute at Health ONE

Denver, Colorado, 80218, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06511, United States

COMPLETED

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Roswell Park

Buffalo, New York, 14263, United States

RECRUITING

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Columbia University Medical Center

New York, New York, 10032, United States

RECRUITING

Memorial Slone Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

NEXT Oncology - Austin

Austin, Texas, 78758, United States

ACTIVE NOT RECRUITING

NEXT Oncology - Dallas

Dallas, Texas, 75039, United States

ACTIVE NOT RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

START Moutain Region

West Valley City, Utah, 84119, United States

COMPLETED

NEXT Oncology - Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

The Kinghorn Cancer Center, St. Vincent's Health Network

Darlinghurst, New South Wales, 2010, Australia

RECRUITING

Scientia Clinical Research, Ltd

Randwick, New South Wales, 2031, Australia

COMPLETED

Gallipoli Medical Research Centre- Greenslopes Private Hospital

Greenslopes, Queensland, 120, Australia

RECRUITING

Southern Oncology Research Unit

Adelaide, South Australia, 5042, Australia

RECRUITING

Cabrini Health Limited

Malvern, Victoria, 3144, Australia

RECRUITING

Cabrini Hospital

Malvern, Victoria, 3144, Australia

RECRUITING

MeSH Terms

Conditions

Neoplasms; Melanoma; Glioma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial

Central Study Contacts

CMO

CONTACT

617-468-4292; info@nestedtx.com

Ann Marie Kennedy

CONTACT

919-427-4225; amkennedy@nestedtx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2024
• First Posted: March 22, 2024
• Study Start: April 9, 2024
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2029
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (17); AU (6)