Actively Recruiting
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 Subjects With Solid Tumors Harboring Genetic Alterations in the MAPK Pathway and Other Solid Tumors
Led by Nested Therapeutics, Inc · Updated on 2026-04-20
230
Participants Needed
23
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the safety, pharmacokinetics, and preliminary effectiveness of NST-628, an oral drug targeting the MAPK pathway, in adults with advanced solid tumors that have specific genetic mutations and have exhausted standard treatments. This Phase 1, open-label, multi-center study includes patients with tumors dependent on the MAPK pathway, such as melanoma and glioma, aiming to find a suitable dose and observe tumor responses. The study has two parts: Part A involves dose escalation where increasing doses of NST-628 are given once daily in 28-day cycles to determine the maximum tolerated dose and the recommended dose for expansion. Part B involves dose expansion with several cohorts of patients harboring specific MAPK pathway mutations receiving the recommended dose to further assess safety and tumor response. Dose adjustments may be made based on observed effects. Participants will undergo regular assessments including safety evaluations, tumor response measurements using standardized criteria, and pharmacokinetic analyses throughout the study, which lasts about one year on average for primary outcomes and up to two years for survival monitoring. Tumor tissue samples are required, and patients will be followed until the last visit of the final participant. Safety, tumor response, progression-free survival, overall survival, and drug behavior in the body are key outcomes measured.
CONDITIONS
Brief Title
A Study to Investigate the Safety and Efficacy of NST-628 Oral Tablets in Subjects With Solid Tumors
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older at the time of informed consent
- Histologically or cytologically confirmed metastatic or locally advanced solid tumor with no effective standard therapy or not suitable for standard treatment
- Part A: Any solid tumor with RAS/MAPK pathway genetic alteration or tumor dependence
- Part B: Diagnosis of specific solid tumors with activating NRAS, KRAS, or select BRAF mutations, including melanoma and glioma
- Newly obtained or archived tumor tissue available
- Measurable disease per RECIST Version 1.1 or standard assessment for tumor type (Part B)
- Performance status: ECOG 0 or 1 for solid tumors other than glioma; Karnofsky ≥ 70 and ECOG 0 or 1 for glioma
- Adequate organ function
- Ability to understand and voluntarily sign informed consent
- Life expectancy of at least 12 weeks
You will not qualify if you...
- Conditions interfering with oral intake or intestinal absorption of NST-628
- History or current significant retinal pathology increasing risk of retinal vein occlusion (RVO)
- History or evidence of cardiovascular risk
- Pneumonitis or interstitial lung disease within 6 months before starting treatment
- Prior treatment with MEK or BRAF inhibitors (Part B)
- Untreated or symptomatic central nervous system metastases
- Chemotherapy, radiation, gene therapy, vaccine therapy, or anti-cancer antibodies within 28 days before treatment start
- Targeted small molecule agents within 14 days or five half-lives before treatment start
- Pregnant or breastfeeding females
- Refusal to use effective contraception during and for 6 months after the trial (fertile patients)
- Serious or unstable systemic disorders incompatible with the study
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Repeated 28-day cycles until disease progression or discontinuation
Participants receive escalating doses of NST-628 oral tablets once daily in 28-day cycles to determine the maximum tolerated dose and recommended dose for expansion. Following dose escalation, participants receive the recommended dose to evaluate safety and tumor response.
Visits occur regularly during each 28-day treatment cycle
Duration - Up to 2 years after treatment completion
Participants are monitored for safety, tumor response, progression-free survival, overall survival, and pharmacokinetics of NST-628 after treatment ends.
Periodic visits over the follow-up period
Trial Site Locations
Total: 23 locations
1
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94158
Actively Recruiting
2
UCLA Hematology/Oncology
Westwood, Los Angeles, California, United States, 90024
Actively Recruiting
3
Sarah Cannon Research Institute at Health ONE
Denver, Colorado, United States, 80218
Actively Recruiting
4
Yale Cancer Center
New Haven, Connecticut, United States, 06511
Completed
5
Moffitt Cancer Center
Tampa, Florida, United States, 33612
Actively Recruiting
6
Roswell Park
Buffalo, New York, United States, 14263
Actively Recruiting
7
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, United States, 10016
Actively Recruiting
8
Columbia University Medical Center
New York, New York, United States, 10032
Actively Recruiting
9
Memorial Slone Kettering Cancer Center
New York, New York, United States, 10065
Actively Recruiting
10
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
Actively Recruiting
11
SCRI Oncology Partners
Nashville, Tennessee, United States, 37203
Actively Recruiting
12
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Actively Recruiting
13
NEXT Oncology - Austin
Austin, Texas, United States, 78758
Active, Not Recruiting
14
NEXT Oncology - Dallas
Dallas, Texas, United States, 75039
Active, Not Recruiting
15
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
16
START Moutain Region
West Valley City, Utah, United States, 84119
Completed
17
NEXT Oncology - Virginia
Fairfax, Virginia, United States, 22031
Actively Recruiting
18
The Kinghorn Cancer Center, St. Vincent's Health Network
Darlinghurst, New South Wales, Australia, 2010
Actively Recruiting
19
Scientia Clinical Research, Ltd
Randwick, New South Wales, Australia, 2031
Completed
20
Gallipoli Medical Research Centre- Greenslopes Private Hospital
Greenslopes, Queensland, Australia, 120
Actively Recruiting
21
Southern Oncology Research Unit
Adelaide, South Australia, Australia, 5042
Actively Recruiting
22
Cabrini Health Limited
Malvern, Victoria, Australia, 3144
Actively Recruiting
23
Cabrini Hospital
Malvern, Victoria, Australia, 3144
Actively Recruiting
Research Team
C
CMO
A
Ann Marie Kennedy
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
1
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here