Trial Title:
A Study to Investigate the Safety and Efficacy of NST-628 Oral Tablets in Subjects with Solid Tumors
NCT ID:
NCT06326411
Condition:
Oncology
MEK Mutation
RAF Gene Mutation
Ras (KRAS or NRAS) Gene Mutation
Melanoma
NSCLC
Glioma
Solid Tumor, Adult
MAPK Pathway Gene Mutation
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
RAS
MEK
RAF
solid tumor
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
NST-628
Description:
NST-628 is a small molecule non-covalent pan-RAF/MEK dual molecular glue targeting RAF
and MEK nodes of MAPK pathway.
Arm group label:
Part A Dose Escalation and Part B Dose Expansion
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.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Subjects are eligible to be included in the study only if all of the following criteria
apply:
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:
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
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
Exclusion Criteria:
Subjects are excluded from the study if any of the following criteria apply:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Roswell Park
Address:
City:
Buffalo
Zip:
14263
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kimberly Benczkowski
Phone:
1-800-767-9355
Phone ext:
1073
Email:
Kimberly.Benczkowski@roswellpark.org
Contact backup:
Last name:
Igor Puzanov, MD
Facility:
Name:
Columbia University Medical Center
Address:
City:
New York
Zip:
10032
Country:
United States
Status:
Recruiting
Contact:
Last name:
Nurse Navigation Team
Phone:
212-342-5162
Email:
cancerclinicaltrials@cumc.columbia.edu
Contact backup:
Last name:
Benjamin Herzberg, MD
Facility:
Name:
NEXT Oncology - Austin
Address:
City:
Austin
Zip:
78758
Country:
United States
Status:
Recruiting
Contact:
Last name:
Brianna Flores
Phone:
210-580-9521
Email:
bflores@nextoncology.com
Contact backup:
Last name:
Andrea Vandross, MD
Facility:
Name:
NEXT Oncology - Dallas
Address:
City:
Dallas
Zip:
75039
Country:
United States
Status:
Recruiting
Contact:
Last name:
Erica Torres
Phone:
210-610-5205
Email:
etorres@nextoncology.com
Contact backup:
Last name:
Naga Cheedella, MD
Facility:
Name:
START Moutain Region
Address:
City:
West Valley City
Zip:
84119
Country:
United States
Status:
Recruiting
Contact:
Last name:
Marie Asay
Phone:
801-907-4770
Email:
marie.asay@startthecure.com
Contact backup:
Last name:
William McKean, MD
Facility:
Name:
NEXT Oncology - Virginia
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Contact:
Last name:
Blake Patterson
Phone:
703-783-4505
Email:
bpatterson@nextoncology.com
Contact backup:
Last name:
Mohamad Salkeni, MD
Facility:
Name:
Scientia Clinical Research, Ltd
Address:
City:
Rand
Zip:
2031
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Shiena Lemin
Phone:
+61 2 9382 5800
Email:
ethics@scientiaclinicalresearch.com.au
Contact backup:
Last name:
Charlotte Lemech, MD
Facility:
Name:
The Kinghorn Cancer Center, St. Vincent's Health Network
Address:
City:
Sidney
Zip:
2010
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Jia (Jenny) Liu, MD
Email:
SVHS.CancerResearch@svha.org.au
Contact backup:
Last name:
Jia (Jenny) Liu, MD
Facility:
Name:
Gallipoli Medical Research Centre- Greenslopes Private Hospital
Address:
City:
Greenslopes
Zip:
120
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Sarah McLennan
Email:
Enquiries.gmrf@ramsayhealth.com.au
Contact backup:
Last name:
Victoria Atkinson, MD
Facility:
Name:
Southern Oncology Research Unit
Address:
City:
Adelaide
Zip:
5042
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Meggan O'Riley
Email:
Meggan.ORiley@socru.org.au
Contact backup:
Last name:
Ganessan Kichenadasse, MD
Start date:
April 9, 2024
Completion date:
November 2029
Lead sponsor:
Agency:
Nested Therapeutics, Inc
Agency class:
Industry
Source:
Nested Therapeutics, Inc
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06326411
