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

Phase 1RecruitingNCT07361562

Cogent Biosciences, Inc.100 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

100

Conditions

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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

Time frame: 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)

Time frame: Approximately 6 months

Secondary Outcomes

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)

Time frame: Approximately 7 months

Pharmacokinetics [Part A]

Area under the concentration-time curve (AUC) in participants with ERBB2 altered advanced solid tumors

Time frame: Approximately 28 days

Pharmacokinetics [Part A]

Maximum observed concentration (Cmax) in participants with ERBB2 altered advanced solid tumors

Time frame: Approximately 28 days

Pharmacokinetics [Part A]

Observed concentration at pre-dose (Ctrough)

Time frame: Approximately 28 days

Pharmacokinetics [Part A)

Time to measure concentration (Tmax)

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Approximately 6 months

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

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts