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

Cogent Biosciences

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumor, Adult; ERBB2 Gene Amplification; HER2 Overexpression; HER2; Non-Small Cell Lung Cancer; ERBB2 Altered Breast Cancer

Treatments: Drug: CGT4255

Study type: Interventional

Funder types: Industry

Identifiers

NCT07361562

CGT4255-25-101

Details and patient eligibility

About

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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100 participants in 3 patient groups

Dose Escalation

Experimental group

Description:

Part A: Dose Escalation Multiple doses of CGT4255 for oral administration

Treatment:

Drug: CGT4255

Signal Seeking and Dose Escalation

Experimental group

Description:

Part B: Signal Seeking and Dose Optimization Oral dose(s) of CGT4255 at the selected dose levels determined in Phase 1

Treatment:

Drug: CGT4255

Signal Seeking

Experimental group

Description:

Part C: Includes signal seeking. Participants will receive CGT4255 at a dose level selected based on data from Part A

Treatment:

Drug: CGT4255