NST-628 for Cancer

(NST-628 Trial)

Recruiting at 26 trial locations

Overseen By Ann Marie Kennedy

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nested Therapeutics, Inc

Must not be taking: MEK inhibitors, BRAF inhibitors

Disqualifiers: Retinal pathology, Cardiovascular risk, ILD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

230 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NST-628 for people with advanced solid tumors that have certain genetic changes. The main goal is to determine the safety of NST-628 and its effectiveness against these tumors. The trial consists of two parts: the first part will establish the best dose, and the second part will focus on specific tumor types, such as certain melanomas and other cancers with genetic alterations in the MAPK pathway. The trial seeks adults whose cancer treatments no longer work or aren't tolerated and who have specific genetic markers in their tumors. As a Phase 1 trial, this research aims to understand how NST-628 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain cancer treatments before starting, such as chemotherapy, radiation, and targeted small molecule agents, for a specific period. However, it doesn't specify about other medications, so you should discuss your current medications with the trial team.

Is there any evidence suggesting that NST-628 is likely to be safe for humans?

Research shows that NST-628 targets specific cancer pathways. This treatment is being tested in patients with advanced solid tumors. In early studies, NST-628 showed promise in models with RAS- and RAF-driven cancers, which are genetic changes found in many tumors.

Safety is a key focus of the trials. The trials aim to find the best dose of NST-628 that patients can handle without serious side effects. Researchers are studying how the body reacts to different doses to determine the safest amount to use.

Since this trial is in the early phase, the treatment's safety remains under close review. While NST-628 has potential, researchers are still learning about patient tolerance. As the study progresses, they will continue to gather safety data to ensure it is well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about NST-628 because it targets genetic mutations directly involved in cancer growth, unlike many standard treatments that often have a broader focus. Specifically, NST-628 is designed to address NRAS and KRAS mutations, as well as certain BRAF alterations, which are common drivers in various advanced solid tumors, including melanoma and glioma. This targeted approach could potentially offer more effective treatment with fewer side effects, providing new hope for patients with these specific genetic profiles.

What evidence suggests that NST-628 might be an effective treatment for advanced solid tumors?

Research has shown that NST-628, which participants in this trial will receive, could be a promising treatment for advanced solid tumors with certain genetic changes. This drug targets a specific pathway in the body that is often overactive in cancers with NRAS, KRAS, or BRAF mutations. Studies have found that the body absorbs and utilizes NST-628 effectively. Early findings suggest it can slow tumor growth in these types of cancers. Although information from human studies remains limited, the initial results are encouraging and show potential for helping patients with no other treatment options. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have mutations in the MAPK pathway and who've run out of standard treatment options. It's open to those over 18 or at legal consent age, with certain types of genetic alterations like NRAS or BRAF mutations, and requires a confirmed diagnosis through tissue samples.

Inclusion Criteria

Understand and voluntarily sign an Institutional Review Board/Independent Ethics Committee-approved informed consent form prior to any study-specific evaluation

My advanced cancer has no standard treatment options left, or I can't tolerate them.

My organs are functioning well.

Exclusion Criteria

I have a history of heart problems or am at risk for heart disease.

I have previously been treated with a MEK or BRAF inhibitor.

I haven't had cancer treatments like chemotherapy or radiation in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Part A)

Participants receive escalating doses of NST-628 to determine the maximum tolerated dose (MTD) in 28-day cycles

28 days per cycle

Dose Expansion (Part B)

Participants receive NST-628 at the recommended dose for expansion (RDE) to evaluate safety and objective tumor response rate

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• NST-628

Trial Overview The study tests NST-628 oral tablets' safety and effectiveness on patients with specific solid tumors. It's an early-stage (Phase 1), non-randomized trial where all participants receive multiple doses of NST-628 to assess its impact on their cancer.

How Is the Trial Designed?

Group I: Part A Dose Escalation and Part B Dose Expansion Experimental Treatment 1 Intervention

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

NST-628 is already approved in United States for the following indications:

Approved in United States as NST-628 for:

• Advanced solid tumors with MAPK pathway mutations

Who Is Running the Clinical Trial?

Nested Therapeutics, Inc

Lead Sponsor

Trials

1

Recruited

230+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06326411

A Study to Investigate the Safety and Efficacy of NST-628 ... 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 ...

2. clinicaltrial.be clinicaltrial.be/en/details/430754?per_page=100&only_recruiting=1&only_eligible=0

A Study to Investigate the Safety and Efficacy of NST-628... 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11215411/

The Pan-RAF–MEK Nondegrading Molecular Glue NST-628 ... With superior pharmacokinetic and pharmacodynamic properties, our data show that NST-628 is positioned as a novel, potent, and tolerable single-agent inhibitor ...

4. uclahealth.org uclahealth.org/clinical-trials/study-investigate-safety-and-efficacy-nst-628-oral-tablets

A Study to Investigate the Safety and Efficacy of NST-628 ... This is a two-part Phase 1, open label, multi-center, single arm, non-randomized, multiple dose, safety, pharmacokinetic (PK) and preliminary efficacy study

5. nestedtx.com nestedtx.com/wp-content/uploads/2024/04/AACR-NDOH-NestedTx.pdf

NST-628 is a Novel, Potent, Fully Brain-Penetrant MAPK ... Polyclonal resistance observed for KRAS inhibitors in the clinic. NST-628 MOI is effective for these mutant tumors. Mutant-specific. KRAS inhibitors have ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06326411

A Study to Investigate the Safety and Efficacy of NST-628 ... 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 ...

7. trialx.com trialx.com/clinical-trials/listings/290322/a-study-to-investigate-the-safety-and-efficacy-of-nst-628-oral-tablets-in-subjects-with-solid-tumors/?&radius=50

A Study to Investigate the Safety and Efficacy of NST-628 ... Part A will estimate the maximum tolerated dose (MTD) in dose escalation cohorts in patients with advanced solid tumors for whom no standard ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02263-4/fulltext

678TiP A phase I, first-in-human, dose escalation and ... NST-628-001 is a global Phase 1, open-label, single-arm, 2-part study to investigate safety, pharmacokinetics, and preliminary efficacy of the orally ...

9. cancer.columbia.edu cancer.columbia.edu/cancer-types-care/clinical-trials/find-clinical-trial/phase-1-open-label-single-arm-two-part-study-investigate-safety-pharmacokinetics-andpreliminary-efficacy-pan-raf-mek-glue-nst-628-oral-tablets-subjects-solid-tumorsharboring-genetic-alterations-mapk

Phase 1, open label single-arm two-part study to investigate ... The purpose of this study is to find out if, and at what dose, NST-628 can safely treat solid cancers in patients who have no other treatment options left.