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

NCT07361562 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CGT4255-25-101
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 6

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.

Conditions

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

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

Outcome Measures

Primary Outcomes (2)

• 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

  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)

  Approximately 6 months

Secondary Outcomes (10)

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

  Approximately 7 months

• Pharmacokinetics [Part A]

  Approximately 28 days

• Pharmacokinetics [Part A]

  Approximately 28 days

• Pharmacokinetics [Part A]

  Approximately 28 days

• Pharmacokinetics [Part A)

  Approximately 28 days

Study Arms (3)

Dose Escalation

EXPERIMENTAL

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

Drug: CGT4255

Signal Seeking and Dose Escalation

EXPERIMENTAL

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

Drug: CGT4255

Signal Seeking

EXPERIMENTAL

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

Drug: CGT4255

Interventions

CGT4255 DRUG

CGT4255 Daily Oral Administration

Dose Escalation; Signal Seeking; Signal Seeking and Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Cogent Biosciences, Inc.: lead

Study Sites (6)

START Midwest

Grand Rapids, Michigan, 49546, United States

RECRUITING

NYU Langone

New York, New York, 10016, United States

RECRUITING

Tennessee Oncology

Nashville, Tennessee, 37203, United States

RECRUITING

NEXT Oncology Texas

Austin, Texas, 78758, United States

RECRUITING

START Mountain Region

West Valley City, Utah, 84119, United States

RECRUITING

NEXT Oncology Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Cogent Biosciences, Inc

CONTACT

617-945-5576; trialinfo@cogentbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: December 3, 2025
• First Posted: January 23, 2026
• Study Start: December 30, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (6)