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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer; ERBB2 Gene Amplification; HER2; Advanced Solid Tumor, Adult; HER2 Overexpression; ERBB2 Altered Breast Cancer
• Intervention / Treatment: Drug: CGT4255

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Cogent Biosciences, Inc; Phone Number: 617-945-5576; Email: trialinfo@cogentbio.com

Study Locations

• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • Start Midwest
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology
  • Texas
    • Austin, Texas, United States, 78758
      • Recruiting
      • NEXT Oncology Texas
      • Contact: Heather Watson; Phone Number: 737-610-5202; Email: hwatson@nextoncology.com
  • Utah
    • West Valley City, Utah, United States, 84119
      • Recruiting
      • START Mountain Region
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Oncology Virginia
      • Contact: VCS Research Referrals; Email: vcsresearchreferrals@usoncology.com
      • Contact: Phone Number: 703-636-1473

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Part A: Dose Escalation Multiple doses of CGT4255 for oral administration	Drug: CGT4255; CGT4255 Daily Oral Administration
Experimental: Signal Seeking and Dose Escalation; Part B: Signal Seeking and Dose Optimization Oral dose(s) of CGT4255 at the selected dose levels determined in Phase 1	Drug: CGT4255; CGT4255 Daily Oral Administration
Experimental: Signal Seeking; Part C: Includes signal seeking. Participants will receive CGT4255 at a dose level selected based on data from Part A	Drug: CGT4255; CGT4255 Daily Oral Administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Part B and C]	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)	Approximately 7 months
Pharmacokinetics [Part A]	Area under the concentration-time curve (AUC) in participants with ERBB2 altered advanced solid tumors	Approximately 28 days
Pharmacokinetics [Part A]	Maximum observed concentration (Cmax) in participants with ERBB2 altered advanced solid tumors	Approximately 28 days
Pharmacokinetics [Part A]	Observed concentration at pre-dose (Ctrough)	Approximately 28 days
Pharmacokinetics [Part A)	Time to measure concentration (Tmax)	Approximately 28 days
Disease Response [Part A]	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)	Approximately 6 months
Disease Response [Part A]	Disease control rate (DCR), as determined by overall confirmed CR + confirmed PR + stable disease (SD) based on Investigator assessment using whole-body RECIST v1.1	Approximately 6 months
Disease Response [Part B and Part C]	Disease Control Rate (DCR), determined by overall confirmed CR + confirmed PR +SD based on Investigator assessment using whole body RECIST v1.1	Approximately 6 months
Disease Response [Part B and Part C]	Duration of Response (DOR), defined as time from first confirmed response (CR or PR) to the date of progressive disease (PD) or death from any cause, whichever occurs earlier	Approximately 6 months
Disease Response [Part B and Part C]	Progression- free survival (PFS), defined as the time from the date of the first dose of study drug (Part B run-in and Part C)/ randomization (Part B randomized cohort) until the date of PD, based on Investigator assessment using whole body RECIST v1.1, or death from any cause, whichever comes earlier	Approximately 6 months

Collaborators and Investigators

• Sponsor: Cogent Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: December 3, 2025
• First Submitted That Met QC Criteria: January 22, 2026
• First Posted (Actual): January 23, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: HER2; Advanced Solid Tumors; Investigational Drug; HER2 Protein Overexpression; Phase 1/1b; ERBB2 genetic alterations; 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
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: CGT4255-25-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No