RECRUITING

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

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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.

Official Title

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

Quick Facts

Study Start:2024-04-09

Study Completion:2029-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06326411

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
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: 1. Activating NRAS mutations 2. Select BRAF alterations 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	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

Inclusion Criteria

Exclusion Criteria

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:
1. Activating NRAS mutations
2. Select BRAF alterations
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

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

Contacts and Locations

Study Contact

CMO

CONTACT

617-468-4292

info@nestedtx.com

Ann Marie Kennedy

CONTACT

919-427-4225

amkennedy@nestedtx.com

Study Locations (Sites)

Roswell Park

Buffalo, New York, 14263

United States

Columbia University Medical Center

New York, New York, 10032

United States

NEXT Oncology - Austin

Austin, Texas, 78758

United States

NEXT Oncology - Dallas

Dallas, Texas, 75039

United States

START Moutain Region

West Valley City, Utah, 84119

United States

NEXT Oncology - Virginia

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: Nested Therapeutics, Inc

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-04-09

Study Completion Date2029-11

Study Record Updates

Study Start Date2024-04-09

Study Completion Date2029-11

Terms related to this study

Keywords Provided by Researchers

RAS
MEK
RAF
solid tumor

Additional Relevant MeSH Terms

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