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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy 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.
Primary outcome measure(s)
Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Part A] — 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
Overall Response Rate [Part B and Part C] — 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)
Trial sites (15)
Facility
City
Region
Status
HonorHealth Research Institute
Scottsdale
Arizona
Recruiting
Mayo Scottsdale
Scottsdale
Arizona
Recruiting
Yale Cancer Center
New Haven
Connecticut
Recruiting
Mayo Jacksonville
Jacksonville
Florida
Recruiting
Northwestern University
Chicago
Illinois
Recruiting
LSU Health Sciences Center School of Medicine
New Orleans
Louisiana
Recruiting
START Midwest
Grand Rapids
Michigan
Recruiting
Mayo Rochester
Rochester
Minnesota
Recruiting
Washington University School of Medicine - Siteman Cancer Center
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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