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RecruitingInterventionalPhase 1

A Study of a Selective ERBB2 Inhibitor, CGT4255, in Patients With Advanced Solid Tumors With ERBB2 Genetic Alterations or HER2 Overexpression

NCT ID: NCT07361562Sponsor: Cogent Biosciences, Inc.Last updated: 2026-02-27

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.

Arms & interventions

  • DrugCGT4255

    CGT4255 Daily Oral Administration

Outcome measures

Primary

  • Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Part A]

    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

    Time frame: 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)

    Time frame: Approximately 6 months

Secondary

  • Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Part B and C]

    Time frame: Approximately 7 months

  • Pharmacokinetics [Part A]

    Time frame: Approximately 28 days

  • Pharmacokinetics [Part A]

    Time frame: Approximately 28 days

  • Pharmacokinetics [Part A]

    Time frame: Approximately 28 days

  • Pharmacokinetics [Part A)

    Time frame: Approximately 28 days

  • Disease Response [Part A]

    Time frame: Approximately 6 months

  • Disease Response [Part A]

    Time frame: Approximately 6 months

  • Disease Response [Part B and Part C]

    Time frame: Approximately 6 months

  • Disease Response [Part B and Part C]

    Time frame: Approximately 6 months

  • Disease Response [Part B and Part C]

    Time frame: Approximately 6 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 locations (6)

START Midwest

Grand Rapids, Michigan, 49546

Recruiting

NYU Langone

New York, New York, 10016

Recruiting

Tennessee Oncology

Nashville, Tennessee, 37203

Recruiting

NEXT Oncology Texas

Austin, Texas, 78758

Recruiting

START Mountain Region

West Valley City, Utah, 84119

Recruiting

NEXT Oncology Virginia

Fairfax, Virginia, 22031

Recruiting