ACTIVE_NOT_RECRUITING

ELVN-002 in HER2 Mutant Non-Small Cell Lung Cancer

Conditions

HER2 Mutant Non-small Cell Lung Cancer HER2-positive Metastatic Breast Cancer HER2 Gene Mutation HER2 Amplification HER2 genetic alterations HER2 mutation ELVN-002 Non-small cell lung cancer HER-2 positive metastatic breast cancer Enhertu trastuzumab emtansine fam-trastuzumab deruxtecan-nxki Kadcyla

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The goal of this clinical trial is to test ELVN-002 in people with cancers that have an abnormal HER2 gene. The main question the trial aims to answer is if ELVN-002 is safe and tolerable at different doses. A second main question is to evaluate the concentration of ELVN-002 in the blood at different doses and to see how this correlates with safety and see how the concentration of drug changes over time. The third main question is to see if ELVN-002 works to shrink cancers that have HER2 genetic abnormalities, particularly non-small cell lung cancer.

Official Title

A Phase 1a/1b Study of ELVN-002 for the Treatment of Patients With HER2 Mutant Non-Small Cell Lung Cancer

Quick Facts

Study Start:2023-03-20

Study Completion:2026-07

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05650879

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Pathologically documented advanced stage solid tumor * Progressed following all standard treatment or not appropriate for standard treatment * HER2 mutation, HER2 amplification or HER2 positive based on local testing * Pathologically documented unresectable and/or metastatic non-squamous NSCLC * HER2 mutation identified by tissue (fresh or archival) or ctDNA. Local testing for up to 20 patients the remainder centrally confirmed. * Measurable disease * No known epidermal growth factor receptor (EGFR), ROS1, anaplastic lymphoma kinase (ALK), or BRAF V600E mutation * Progressed after receiving at least 1 prior systemic therapy including a platinum-based chemotherapy with or without immunotherapy, or not appropriate for standard treatment. * No prior HER2 tyrosine kinase inhibitor. Prior HER2 directed antibodies or anti-body drug conjugates are allowed * No limit on prior number of therapies * Pathologically documented advanced stage NSCLC * Progressed after receiving at least 1 prior systemic therapy. * HER2 mutation based on local/historical testing of tissue or circulating tumor DNA * No known EGFR, ROS1, ALK, or BRAF V600E mutation * No prior T-DXd * No clinically severe pulmonary compromise * No limit on prior number of therapies * Documented HER2 positive (Immunohistochemical \[IHC\] 3+ or IHC2+/in situ hybridization (ISH+) breast cancer * Must have previously received trastuzumab, a taxane, and T-DXd (if available and appropriate) in the metastatic setting. * No limit on prior number of therapies * No prior T-DM1 * Eastern Cooperative Oncology Group performance status of 0-1 * Left ventricular ejection fraction ≥ 50% * Platelet count ≥ 100 x 109/L * Hemoglobin ≥ 8.5 g/dL * Absolute neutrophil count ≥1.0 x 109/L * Total bilirubin \< 1.5 times upper limit of normal range (ULN), except for patients with Gilbert's syndrome * Aspartate aminotransferase (AST), alanine aminotransferase (ALT) \< 3 times ULN. In the setting of liver metastases \< 5 times ULN. * Creatinine clearance ≥ 60 mL/minute * Severe cardiac arrhythmias, requiring treatment, symptomatic congestive heart failure, myocardial infarction within 28 days prior to first dose, or unstable angina. * Another active malignancy within 2 years except basal cell skin cancer and carcinoma in situ treated curatively * Active or chronic liver disease * Active infection requiring systemic therapy within 14 days before the first dose * Brain lesion requiring immediate local therapy * Leptomeningeal disease * Uncontrolled seizures * Corrected QT interval (QTc) of \>470 milliseconds (ms) females or \>450 ms for males by Fridericia (QTcF)	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion Criteria

* Pathologically documented advanced stage solid tumor
* Progressed following all standard treatment or not appropriate for standard treatment
* HER2 mutation, HER2 amplification or HER2 positive based on local testing
* Pathologically documented unresectable and/or metastatic non-squamous NSCLC
* HER2 mutation identified by tissue (fresh or archival) or ctDNA. Local testing for up to 20 patients the remainder centrally confirmed.
* Measurable disease
* No known epidermal growth factor receptor (EGFR), ROS1, anaplastic lymphoma kinase (ALK), or BRAF V600E mutation
* Progressed after receiving at least 1 prior systemic therapy including a platinum-based chemotherapy with or without immunotherapy, or not appropriate for standard treatment.
* No prior HER2 tyrosine kinase inhibitor. Prior HER2 directed antibodies or anti-body drug conjugates are allowed
* No limit on prior number of therapies
* Pathologically documented advanced stage NSCLC
* Progressed after receiving at least 1 prior systemic therapy.
* HER2 mutation based on local/historical testing of tissue or circulating tumor DNA
* No known EGFR, ROS1, ALK, or BRAF V600E mutation
* No prior T-DXd
* No clinically severe pulmonary compromise
* No limit on prior number of therapies
* Documented HER2 positive (Immunohistochemical \[IHC\] 3+ or IHC2+/in situ hybridization (ISH+) breast cancer
* Must have previously received trastuzumab, a taxane, and T-DXd (if available and appropriate) in the metastatic setting.
* No limit on prior number of therapies
* No prior T-DM1
* Eastern Cooperative Oncology Group performance status of 0-1
* Left ventricular ejection fraction ≥ 50%
* Platelet count ≥ 100 x 109/L
* Hemoglobin ≥ 8.5 g/dL
* Absolute neutrophil count ≥1.0 x 109/L
* Total bilirubin \< 1.5 times upper limit of normal range (ULN), except for patients with Gilbert's syndrome
* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) \< 3 times ULN. In the setting of liver metastases \< 5 times ULN.
* Creatinine clearance ≥ 60 mL/minute
* Severe cardiac arrhythmias, requiring treatment, symptomatic congestive heart failure, myocardial infarction within 28 days prior to first dose, or unstable angina.
* Another active malignancy within 2 years except basal cell skin cancer and carcinoma in situ treated curatively
* Active or chronic liver disease
* Active infection requiring systemic therapy within 14 days before the first dose
* Brain lesion requiring immediate local therapy
* Leptomeningeal disease
* Uncontrolled seizures
* Corrected QT interval (QTc) of \>470 milliseconds (ms) females or \>450 ms for males by Fridericia (QTcF)

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Study Locations (Sites)

University of Colorado - Anschutz Medical Campus - PPDS

Aurora, Colorado, 80045

United States

Advent Health Orlando

Orlando, Florida, 32804

United States

BRCR Medical Center Inc

Plantation, Florida, 33322

United States

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

United States

NEXT/Virginia Cancer Specialists

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: Enliven Therapeutics

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-03-20

Study Completion Date2026-07

Study Record Updates

Study Start Date2023-03-20

Study Completion Date2026-07

Terms related to this study

Keywords Provided by Researchers

HER2 genetic alterations
HER2 mutation
ELVN-002
Non-small cell lung cancer
HER-2 positive metastatic breast cancer
Enhertu
trastuzumab emtansine
fam-trastuzumab deruxtecan-nxki
Kadcyla

Additional Relevant MeSH Terms

HER2 Mutant Non-small Cell Lung Cancer
HER2-positive Metastatic Breast Cancer
HER2 Gene Mutation
HER2 Amplification