Advanced Solid Tumor, Adult, ERBB2 Altered Breast Cancer, ERBB2 Gene Amplification, HER2, HER2 Overexpression, Non-Small Cell Lung Cancer
Conditions
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
Brief 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.
Interventions
DRUGCGT4255
CGT4255 Daily Oral Administration
Sponsors
Cogent Biosciences, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Part B and C] | 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) |
| Pharmacokinetics [Part A] | Approximately 28 days | Area under the concentration-time curve (AUC) in participants with ERBB2 altered advanced solid tumors |
| Pharmacokinetics [Part A) | Approximately 28 days | Time to measure concentration (Tmax) |
| Disease Response [Part A] | 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) |
| Disease Response [Part B and Part C] | 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 |
Countries
United States
Contacts
CONTACTCogent Biosciences, Inc
Outcome results
None listed