Advanced Solid Tumor, AdultPhase 1NCT07361562
A Study of a Selective ERBB2 Inhibitor (CGT4255), in Patients With Advanced Solid Tumors
A Phase 1 study testing CGT4255 in people with Advanced Solid Tumor, Adult and ERBB2 Altered Breast Cancer, run by Cogent Biosciences, Inc. at 15 sites in United States.
Trial summary
This is an open-label, phase 1/1b study evaluating the safety, tolerability, pharmacokinetic (what the body does to the drug), pharmacodynamic (what the drug does to the body), and antitumor activity of CGT4255 in adult participants with advanced solid tumors with ERBB2 alterations or HER2 overexpression. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor, Adult, ERBB2 Altered Breast Cancer, ERBB2 Gene Amplification
- What is being tested?
- CGT4255
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 15 sitesUnited States
- Study dates
- 30 Dec 2025to Nov 2028
- 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
- Have histologically confirmed diagnosis of:
- Part A: Locally advanced, metastatic, and/or unresectable solid tumor with documented ERBB2-activating alteration or NRG1 gene fusion in blood and/or tumor or HER2 overexpression in tumor
- Part B: Locally advanced, metastatic, and/or unresectable NSCLC with documented ERBB2 mutation in blood and/or tumor
- Part C: Locally advanced, metastatic and/or unresectable breast cancer with documented ERBB2 mutation in blood and/or tumor or HER overexpression in tumor
- Have measurable disease per RECIST v1.1.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1 for Part A. For Parts B and C, ECOG Performance Status must be 0 to 2.
- Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits.
Who cannot join
- Received small molecule chemotherapy or anticancer therapies or radiotherapy within certain timeframes before first dose of study drug.
- Major surgeries (eg, craniotomy and thoracotomy) within 4 weeks of the first dose of study drug.
- Treatment with palliative focal radiotherapy (cranial or extracranial) (eg, stereotactic radiosurgery or intensity-modulated radiation therapy) ≤2 weeks before the first dose of study drug; treatment with whole-brain radiotherapy ≤4 weeks before the first dose of study drug.
- Clinically significant cardiac disease.
- Resolution of toxicities from prior therapy to ≤Grade 1 (or baseline), including resolution of clinically significant laboratory abnormalities, before the first dose of study drug.
- Restrictions on use of corticosteroid use to manage neurologic symptoms in different parts of the study.
Trial locations and contacts
15 sites in 1 country. Contact the study team or a site near you to ask about taking part.
15 sites in 1 country
United States15 sites, 15 recruiting
- Recruiting
NEXT Oncology Texas
Austin, Texas, 78758
- Recruiting
Northwestern University
Chicago, Illinois, 60611
- Recruiting
NEXT Oncology Virginia
Fairfax, Virginia, 22031
- Recruiting
START Midwest
Grand Rapids, Michigan, 49546
- Recruiting
Mayo Jacksonville
Jacksonville, Florida, 32209
- Recruiting
START NY Long Island
Lake Success, New York, 11042
- Recruiting
Tennessee Oncology
Nashville, Tennessee, 37203
- Recruiting
Yale Cancer Center
New Haven, Connecticut, 06510
- Recruiting
LSU Health Sciences Center School of Medicine
New Orleans, Louisiana, 70803
- Recruiting
NYU Langone
New York, New York, 10016
- Recruiting
Mayo Rochester
Rochester, Minnesota, 55905
- Recruiting
HonorHealth Research Institute
Scottsdale, Arizona, 85258
- Recruiting
Mayo Scottsdale
Scottsdale, Arizona, 85281
- Recruiting
Washington University School of Medicine - Siteman Cancer Center
St Louis, Missouri, 63110
- Recruiting
START Mountain Region
West Valley City, Utah, 84119
About this study
Official title: A Study of a Selective ERBB2 Inhibitor, CGT4255, in Patients With Advanced Solid Tumors With ERBB2 Genetic Alterations or HER2 Overexpression
This is an open-label, phase 1/1b study evaluating the safety, tolerability, pharmacokinetic (what the body does to the drug), pharmacodynamic (what the drug does to the body), and antitumor activity of CGT4255 in adult participants with advanced solid tumors with ERBB2 alterations or HER2 overexpression.
- Conditions
- Advanced Solid Tumor, Adult, ERBB2 Altered Breast Cancer, ERBB2 Gene Amplification, HER2 Overexpression, Non-Small Cell Lung Cancer, HER2
- Being tested
- CGT4255
- Keywords
- ERBB2 genetic alterations, Investigational Drug, Advanced Solid Tumors, ERBB2 Mutated Non Small Cell Lung Cancer, Mutated Advanced Solid Tumors, ERBB2 Brain Metastases, ERRB2 Point Mutations, ERBB2 Gene Short Variants, ERBB2 Gene Rearrangements, ERBB2 activation alteration, ERBB2 gene copy number amplifications, ERBB2 gene insertions, ERRB2 gene deletions, ERBB2 gene fusions, NRG1 gene fusions, ERBB2 indel, Phase 1/1b, HER2 Protein Overexpression, HER2
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CGT4255Drug
CGT4255 Daily Oral Administration
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation | Experimental | Part A: Dose Escalation Multiple doses of CGT4255 for oral administration Receives: Drug: CGT4255 |
| Signal Seeking and Dose Escalation | Experimental | Part B: Signal Seeking and Dose Optimization Oral dose(s) of CGT4255 at the selected dose levels determined in Phase 1 Receives: Drug: CGT4255 |
| Signal Seeking | Experimental | Part C: Includes signal seeking. Participants will receive CGT4255 at a dose level selected based on data from Part A Receives: Drug: CGT4255 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Part A]
- Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) and AEs leading to dose modifications and dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD) or the maximum evaluated dose (MED) in participants with ERBB2-altered advanced solid tumors
Measured: Approximately 12 months
Overall Response Rate [Part B and Part C]
Overall Response Rate (ORR), determined by confirmed CR + PR of all lesions (intracranial and extracranial), based on Investigator assessment using the whole-body RECIST v1.1 in participants with ERBB2-mutated NSCLC with Brain Metastases (BM) and in participants with ERBB2-mutated or HER2-positive breast cancer with BM ± leptomeningeal disease (LMD)
Measured: Approximately 6 months
Secondary outcomes (10)
Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Part B and C]
Incidence and grade of Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs leading to dose modification in participants with ERBB2-mutated NSCLC with Brain Metastases (BM) and in participants with ERBB2-mutated or HER2-positive breast cancer with BM ± leptomeningeal disease (LMD)
Measured: Approximately 7 months
Pharmacokinetics [Part A]
Area under the concentration-time curve (AUC) in participants with ERBB2 altered advanced solid tumors
Measured: Approximately 28 days
Pharmacokinetics [Part A]
Maximum observed concentration (Cmax) in participants with ERBB2 altered advanced solid tumors
Measured: Approximately 28 days
Pharmacokinetics [Part A]
Observed concentration at pre-dose (Ctrough)
Measured: Approximately 28 days
Pharmacokinetics [Part A)
Time to measure concentration (Tmax)
Measured: Approximately 28 days
Disease Response [Part A]
Overall objective response rate (ORR), as determined by confirmed complete response (CR) + confirmed partial response (PR) of all lesions (intracranial and extracranial) based on Investigator assessment using whole-body Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Measured: Approximately 6 months
Disease Response [Part A]
Disease control rate (DCR), as determined by overall confirmed CR + confirmed PR + stable disease (SD) based on Investigator assessment using whole-body RECIST v1.1
Measured: Approximately 6 months
Disease Response [Part B and Part C]
Disease Control Rate (DCR), determined by overall confirmed CR + confirmed PR +SD based on Investigator assessment using whole body RECIST v1.1
Measured: Approximately 6 months
Disease Response [Part B and Part C]
Duration of Response (DOR), defined as time from first confirmed response (CR or PR) to the date of progressive disease (PD) or death from any cause, whichever occurs earlier
Measured: Approximately 6 months
Disease Response [Part B and Part C]
Progression- free survival (PFS), defined as the time from the date of the first dose of study drug (Part B run-in and Part C)/ randomization (Part B randomized cohort) until the date of PD, based on Investigator assessment using whole body RECIST v1.1, or death from any cause, whichever comes earlier
Measured: Approximately 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2026
- Study start30 Dec 2025
- Primary completionMay 2028 (estimated)
- Study completionNov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid Tumor, AdultStudies 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
- Non-randomised
- Intervention model
- Sequential
- Model description
- Phase 1, Part A evaluating multiple ascending doses. Phase 1b, evaluation of Part A selected doses in 2 cohorts defined by tumor type including a randomized dose optimization design (Part B)
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cogent Biosciences, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07361562
- Sponsor's protocol ID
- CGT4255-25-101
- Status last verified
- Sep 2026
- First submitted
- 3 Dec 2025
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No