A Study of a Selective ERBB2 Inhibitor (CGT4255), in Patients With Advanced Solid Tumors

September 3, 2026 updated by: Cogent Biosciences, Inc.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • Recruiting
        • HonorHealth Research Institute
      • Scottsdale, Arizona, United States, 85281
        • Recruiting
        • Mayo Scottsdale
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Yale Cancer Center
    • Florida
      • Jacksonville, Florida, United States, 32209
        • Recruiting
        • Mayo Jacksonville
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University
    • Louisiana
      • New Orleans, Louisiana, United States, 70803
        • Recruiting
        • LSU Health Sciences Center School of Medicine
    • Michigan
      • Grand Rapids, Michigan, United States, 49546
        • Recruiting
        • START MidWest
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Rochester
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine - Siteman Cancer Center
    • New York
      • Lake Success, New York, United States, 11042
        • Recruiting
        • START NY Long Island
      • New York, New York, United States, 10016
        • Recruiting
        • NYU Langone
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Tennessee Oncology
    • Texas
      • Austin, Texas, United States, 78758
    • Utah
      • West Valley City, Utah, United States, 84119
        • Recruiting
        • START Mountain Region
    • Virginia
      • Fairfax, Virginia, United States, 22031

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Have histologically confirmed diagnosis of:

    1. 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
    2. Part B: Locally advanced, metastatic, and/or unresectable NSCLC with documented ERBB2 mutation in blood and/or tumor
    3. Part C: Locally advanced, metastatic and/or unresectable breast cancer with documented ERBB2 mutation in blood and/or tumor or HER overexpression in tumor
  2. Have measurable disease per RECIST v1.1.
  3. 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.
  4. Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits.

Exclusion Criteria:

  1. Received small molecule chemotherapy or anticancer therapies or radiotherapy within certain timeframes before first dose of study drug.
  2. Major surgeries (eg, craniotomy and thoracotomy) within 4 weeks of the first dose of study drug.
  3. 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.
  4. Clinically significant cardiac disease.
  5. 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.
  6. Restrictions on use of corticosteroid use to manage neurologic symptoms in different parts of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation
Part A: Dose Escalation Multiple doses of CGT4255 for oral administration
Drug: CGT4255
CGT4255 Daily Oral Administration
Experimental: Signal Seeking and Dose Escalation
Part B: Signal Seeking and Dose Optimization Oral dose(s) of CGT4255 at the selected dose levels determined in Phase 1
Drug: CGT4255
CGT4255 Daily Oral Administration
Experimental: Signal Seeking
Part C: Includes signal seeking. Participants will receive CGT4255 at a dose level selected based on data from Part A
Drug: CGT4255
CGT4255 Daily Oral Administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Part A]
Time Frame: Approximately 12 months
1. 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
Approximately 12 months
Overall Response Rate [Part B and Part C]
Time Frame: Approximately 6 months
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)
Approximately 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Part B and C]
Time Frame: Approximately 7 months
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)
Approximately 7 months
Pharmacokinetics [Part A]
Time Frame: Approximately 28 days
Area under the concentration-time curve (AUC) in participants with ERBB2 altered advanced solid tumors
Approximately 28 days
Pharmacokinetics [Part A]
Time Frame: Approximately 28 days
Maximum observed concentration (Cmax) in participants with ERBB2 altered advanced solid tumors
Approximately 28 days
Pharmacokinetics [Part A]
Time Frame: Approximately 28 days
Observed concentration at pre-dose (Ctrough)
Approximately 28 days
Pharmacokinetics [Part A)
Time Frame: Approximately 28 days
Time to measure concentration (Tmax)
Approximately 28 days
Disease Response [Part A]
Time Frame: Approximately 6 months
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)
Approximately 6 months
Disease Response [Part A]
Time Frame: Approximately 6 months
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
Approximately 6 months
Disease Response [Part B and Part C]
Time Frame: Approximately 6 months
Disease Control Rate (DCR), determined by overall confirmed CR + confirmed PR +SD based on Investigator assessment using whole body RECIST v1.1
Approximately 6 months
Disease Response [Part B and Part C]
Time Frame: Approximately 6 months
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
Approximately 6 months
Disease Response [Part B and Part C]
Time Frame: Approximately 6 months
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
Approximately 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cogent Biosciences, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 30, 2025

Primary Completion (Estimated)

May 1, 2028

Study Completion (Estimated)

November 1, 2028

Study Registration Dates

First Submitted

December 3, 2025

First Submitted That Met QC Criteria

January 22, 2026

First Posted (Actual)

January 23, 2026

Study Record Updates

Last Update Posted (Actual)

September 4, 2026

Last Update Submitted That Met QC Criteria

September 3, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CGT4255-25-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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