OncologyPhase 1NST-628NCT06326411
A Study to Investigate the Safety and Efficacy of NST-628 Oral Tablets in Subjects With Solid Tumors
A Phase 1 study testing NST-628 in people with Oncology and MEK Mutation, run by Nested Therapeutics, Inc at 23 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oncology, MEK Mutation, RAF Gene Mutation
- What is being tested?
- NST-628
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 230 participants
- Where
- 23 sitesin 2 countries
- Study dates
- 9 Apr 2024to Nov 2029
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- Melanoma Cohorts:
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- Activating NRAS mutations
- Select BRAF alterations
- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
23 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
23 sites in 2 countries
United States17 sites, 13 recruiting
- Active, not recruiting
NEXT Oncology - Austin
Austin, Texas, 78758
- Recruiting
Roswell Park
Buffalo, New York, 14263
Study Coordinator, 800-767-9355, Askroswell@roswellpark.org
Igor Puzanov, MD
- Active, not recruiting
NEXT Oncology - Dallas
Dallas, Texas, 75039
- Recruiting
Sarah Cannon Research Institute at Health ONE
Denver, Colorado, 80218
844-482-4812
Gerald Falchook, MD, MS
- Recruiting
NEXT Oncology - Virginia
Fairfax, Virginia, 22031
Blake Patterson, 703-783-4505, bpatterson@nextoncology.com
Mohamad Salkeni, MD
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Rabia Khan, 713-563-4667, rkhan@mdanderson.org
Sarina Piha-Paul, MD
- Recruiting
SCRI Oncology Partners
Nashville, Tennessee, 37203
844-482-4812
Meredith McKean, MD, MPH
- Recruiting
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
Angie Boeing, 800-811-8480, CTIP@VUMC.ORG
Jordan D Berlin, MD
- Completed
Yale Cancer Center
New Haven, Connecticut, 06511
- Recruiting
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, 10016
Janice Mehnert, MD
- Recruiting
Columbia University Medical Center
New York, New York, 10032
Nurse Navigation Team, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu
Benjamin Herzberg, MD
- Recruiting
Memorial Slone Kettering Cancer Center
New York, New York, 10065
Monica Chen, MD
- Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
IDDCreferrals@upmc.edu
Jason Luke, MD
- Recruiting
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94158
Phu Lam Clinical Research Manager, 415-818-7994, Phu.Lam@ucsf.com
Virun Monga, MD
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Justin Martin, 813-745-7544, Justin.martin@moffitt.org
ctocutaneous@moffitt.org
- Completed
START Moutain Region
West Valley City, Utah, 84119
- Recruiting
UCLA Hematology/Oncology
Westwood, Los Angeles, California, 90024
Bartosz Chmielowski, MD, 310-794-4955, bchmielowski@mednet.ucla.edu
Bartosz Chmielowski, MD
Australia6 sites, 5 recruiting
- Recruiting
Southern Oncology Research Unit
Adelaide, South Australia, 5042
Meggan O'Riley, Meggan.ORiley@socru.org.au
Ganessan Kichenadasse, MD
- Recruiting
The Kinghorn Cancer Center, St. Vincent's Health Network
Darlinghurst, New South Wales, 2010
Jia (Jenny) Liu, MD, SVHS.CancerResearch@svha.org.au
Jia (Jenny) Liu, MD
- Recruiting
Gallipoli Medical Research Centre- Greenslopes Private Hospital
Greenslopes, Queensland, 120
Sarah McLennan, Enquiries.gmrf@ramsayhealth.com.au
Victoria Atkinson, MD
- Recruiting
Cabrini Health Limited
Malvern, Victoria, 3144
Study Coordinator, clinicaltrials@cabrini.com.au
Prachi Bhave, MD
- Recruiting
Cabrini Hospital
Malvern, Victoria, 3144
Study Coordinator, clinicaltrials@cabrini.com.au
Prachi Bhave, MD
- Completed
Scientia Clinical Research, Ltd
Randwick, New South Wales, 2031
About this study
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
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.
Read the detailed description
The study includes two parts, a dose escalation part (Part A) followed by a dose expansion part (Part B). Part A will estimate the maximum tolerated dose (MTD) in dose escalation cohorts in patients with advanced solid tumors for whom no standard therapy is available in order to establish the recommended dose for expansion (RDE). Successive cohorts of subjects will receive escalating doses of NST-628 orally once daily in 28-day cycles.
Bayesian Optimal Interval (BOIN) method will be used for dose escalation.
Once MTD is reached or dose escalation is stopped prior to reaching MTD and provisional RDE selected, the provisional RDE level will be expanded. If warranted by dose/toxicity/anti-tumor activity observations, additional, lower dose level(s) may also be expanded.
Part B of the study will include up to 6 cohorts of approximately up to 30 subjects each with select MAPK pathway mutant solid tumors enrolled at the RDE in order to explore benefit from treatment as suggested by preclinical findings and will better define the safety profile of NST-628 at the RDE. Additional safety information gathered in Part B may be used to modify the dose recommended for future studies.
The end of the study is the last visit of the last subject.
- Conditions
- Oncology, MEK Mutation, RAF Gene Mutation, Ras (KRAS or NRAS) Gene Mutation, Melanoma, NSCLC
- Being tested
- NST-628
- Keywords
- RAS, MEK, RAF, solid tumor
- Medical subject headings
- Neoplasms, Melanoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NST-628Drug
NST-628 is a small molecule non-covalent pan-RAF/MEK dual molecular glue targeting RAF and MEK nodes of MAPK pathway.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: NST-628 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A and B: Evaluate the safety of NST-628 in patients with advanced solid tumors
Adverse effects
Measured: Through study completion, an average of 1 year
Part A: Determine the recommended dose for expansion of NST-628
Dose limiting toxicities (DLTs)
Measured: 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.
Measured: Through study completion, an average of 1 year
Secondary outcomes (4)
Part A: Evaluate objective tumor response rate
Objective response per RECIST v. 1.1 or other response assessment tool standard for a given tumor type.
Measured: Through study completion, an average of 1 year
Part A and B: Evaluate progression free survival (PFS)
PFS defined as the time to first occurrence of disease progression per RECIST v1.1 (or other response assessment tool standard for a given tumor type) or death
Measured: Through study completion, an average of 1 year
Part A and B: Evaluate overall survival (OS)
Overall survival (OS) defined as the time to death
Measured: Through study completion, an average of 2 years
Part A and B: Characterize the pharmacokinetics of NST-628
NST-628 concentrations in plasma
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2024
- Study start9 Apr 2024
- Primary completionNov 2028 (estimated)
- Study completionNov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OncologyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 230 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nested Therapeutics, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06326411
- Sponsor's protocol ID
- NST-628-001
- Acronym
- NST-628
- Status last verified
- Apr 2026
- First submitted
- 15 Mar 2024
- Last updated
- 20 Apr 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No