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HER2 Mutant Non-small Cell Lung CancerPhase 1HER2NCT05650879

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

A Phase 1 study testing ELVN-002, Fam-Trastuzumab Deruxtecan-Nxki and Trastuzumab emtansine in people with HER2 Mutant Non-small Cell Lung Cancer and HER2-positive Metastatic Breast Cancer, run by Enliven Therapeutics at 39 sites in 7 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ELVN-002, Fam-Trastuzumab Deruxtecan-Nxki and Trastuzumab emtansine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
198 participants
Where
39 sitesin 7 countries
Study dates
20 Mar 2023to Jul 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Phase 1a Monotherapy Dose Escalation and Exploration:
  • 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
  • Phase 1b Monotherapy
  • Pathologically documented unresectable and/or metastatic non-squamous NSCLC
Show all 34Show fewer
  • 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
  • Phase 1a Combination with T-DXd
  • 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
  • Phase 1a Combination Breast Cancer
  • 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
  • All Phases
  • 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

Who cannot join

  • 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)

Trial locations and contacts

39 sites in 7 countries.

39 sites in 7 countries

Spain9 sites

  • START Barcelona Hospital HM Nou Delfos

    Barcelona, 08023

  • Hospital Universitari Vall d'Hebrón

    Barcelona, 08035

  • lnstitut Catala d'Oncologia (ICO) L'Hospitalet, Servicio de Oncologia Medica

    L'Hospitalet de Llobregat, 08908

  • Hospital Universitari Arnau de Vilanova

    Lleida, Lleida, 25198

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid, 28040

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario Virgen Macarena

    Seville, Sevilla, 41009

  • Fundación Instituto Valenciano de Oncología

    Valencia, 46009

  • Hospital Universitari i Politècnic La Fe

    Valencia, 46026

Other trials in Spain

France7 sites

  • EDOG - Institut Bergonie - PPDS

    Bordeaux, Gironde, 33000

  • Centre Francois Baclesse

    Caen, Calvados, 14076

  • Centre Georges François Leclerc

    Dijon, 21079

  • Centre Léon Berard

    Lyon, 69373

  • Hôpital de la Timone Centre d'essais en cancérologie de Marseille (CEPCM-CLIPP)

    Marseille, Bouches-du-Rhône, 13005

  • Hôpital Pontchaillou

    Rennes, Brittany Region, 35033

  • Institut Gustave Roussy (IGR)

    Villejuif, 94805

Other trials in France

Italy6 sites

  • Azienda Ospedaliero Universitaria delle Marche

    Ancona, The Marches, 60126

  • SOC Oncologia Medica e dei Tumori lmmunocorrelati, Centro Di Riferimento Oncologico Di Aviano (CRO) IRCCS

    Aviano, Pordenone, 33081

  • Fondazione del Piemonte per l'Oncologia (IRCCS)

    Candiolo, Piedmont, 10060

  • Fondazione IRCCS San Gerardo dei Tintori

    Monza, Lombardy, 20900

  • Fondazione Policlinico Universitario A. Gemelli

    Roma, 00168

  • Unità Operativa Oncologia medica ed Ematologia

    Rozzano, 20089

Other trials in Italy

South Korea6 sites

  • Gachon University Gil Medical Center

    Incheon

  • Severence Hospital, Yonsei University

    Seoul, 03722

  • Samsung Medical Center

    Seoul, 06351

  • Seoul National University Hospital

    Seoul, 3080

  • Korea University Anam Hospital

    Seoul

  • The Catholic University of Korea, St. Vincent's Hospital

    Suwon, Gyeonggido, 16247

Other trials in South Korea

United States5 sites

  • University of Colorado - Anschutz Medical Campus - PPDS

    Aurora, Colorado, 80045

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • NEXT/Virginia Cancer Specialists

    Fairfax, Virginia, 22031

  • Advent Health Orlando

    Orlando, Florida, 32804

  • BRCR Medical Center Inc

    Plantation, Florida, 33322

Other trials in United States

Australia3 sites

  • Blacktown Hospital

    Darlinghurst, 2010

  • Linear Clinical Research Limited

    Nedlands, Western Australia, 6009

  • Macquarie University Hospital

    Westmead, New South Wales, 2145

Other trials in Australia

Taiwan3 sites

  • Taichung Veterans General Hospital

    Taichung, 40705

  • National Chen Kung University Hospital

    Tainan

  • National Taiwan University Hospital

    Taipei

Other trials in Taiwan

About this study

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

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.

Read the detailed description

There are 4 parts to the trial. Part 1 is a dose escalation with ELVN-002 monotherapy for people with advanced stage solid tumors that have a HER2 mutation, amplification or high HER2 over-expression. Part 2 is an ELVN-002 monotherapy dose exploration where additional people may be enrolled at dose levels that have cleared the dose escalation in Part 1 to further evaluate the safety, tolerability, pharmacokinetics and clinical activity. Part 3 is a dose expansion of ELVN-002 monotherapy which will enroll up to 40 patients people with advanced stage HER2 mutant non-small cell lung cancer. Patients in Part 3 will be randomized 1:1 to receive one of two dose levels.

Part 4 is a combination dose escalation where, based on the results of Part 1 and 2, a combination of ELVN-002 and either fam-trastuzumab deruxtecan-nxki (in HER2 mutant non-small cell lung cancer) or trastuzumab emtansine (in HER2 positive breast cancer) will be evaluated for safety and tolerability.

Being tested
ELVN-002, Fam-Trastuzumab Deruxtecan-Nxki, Trastuzumab emtansine
Keywords
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
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ELVN-002Drug

    capsule

  • Fam-Trastuzumab Deruxtecan-NxkiDrug

    Also called Enhertu, T-DXd

    intravenous

  • Trastuzumab emtansineDrug

    Also called Kadcyla, T-DM1

    intravenous

Study groups in NCT05650879
Study groupRoleWhat they receive
Phase 1a Monotherapy Dose EscalationExperimentalELVN-002 will be administered either once or twice daily. Each cohort of patients will receive a higher dose. ELVN-002 is an oral capsule. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.
Receives: Drug: ELVN-002
Phase 1a Monotherapy Dose ExplorationExperimentalELVN-002 will be administered either once or twice daily. A maximum of 80 patients will enroll in this arm. A maximum of 10 patients may be enrolled at a single dose or tumor type. ELVN-002 is an oral capsule. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.
Receives: Drug: ELVN-002
Phase 1b Monotherapy Dose ExpansionExperimentalELVN-002 will be administered either once or twice daily. A maximum of 40 patients will enroll in this arm. Patients will be randomized 1:1 to one of two dose levels. ELVN-002 is an oral capsule. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.
Receives: Drug: ELVN-002
Phase 1a Combination Dose Escalation with T-DXdExperimentalELVN-002 will be administered either once or twice daily starting on Day 1. ELVN-002 is an oral capsule. Each cohort will receive a higher dose of ELVN-002. All patients in all cohorts will initiate with 5.4mg/kg of intravenous T-DXd once every 3 weeks starting on day 22 of the study. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.
Receives: Drug: ELVN-002; Drug: Fam-Trastuzumab Deruxtecan-Nxki
Phase 1a Combination Dose Escalation with T-DM1ExperimentalELVN-002 will be administered either once or twice daily starting on Day 1. ELVN-002 is an oral capsule. Each cohort will receive a higher dose of ELVN-002. All patients in all cohorts will initiate with 3.6 mg/kg of intravenous T-DM1 once every 3 weeks starting on day 22 of the study. Duration of treatment will be until disease progression or patient discontinues ELVN-002 for another reason.
Receives: Drug: ELVN-002; Drug: Trastuzumab emtansine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of dose limiting toxicities in Phase 1a monotherapy

    Measured: 21 days

  2. Incidence of adverse events in Phase 1a monotherapy

    Measured: 24 months

  3. incidence of laboratory abnormalities in Phase 1a monotherapy

    Measured: 24 months

  4. incidence of ECG abnormalities in Phase 1a monotherapy

    Measured: 24 months

  5. incidence of dose limiting toxicities in Phase 1a combination with fam-trastuzumab deruxtecan (T-DXd)

    Measured: 42 days

  6. Incidence of adverse events in Phase 1a combination with T-DXd

    Measured: 24 months

  7. incidence of laboratory abnormalities in Phase 1a combination with T-DXd

    Measured: 24 months

  8. incidence of ECG abnormalities in Phase 1a combination with T-DXd

    Measured: 24 months

  9. incidence of dose limiting toxicities in Phase 1a combination with trastuzumab emantasine (T-DM1)

    Measured: 42 days

  10. Incidence of adverse events in Phase 1a combination with T-DM1

    Measured: 24 months

  11. incidence of laboratory abnormalities in Phase 1a combination with T-DM1

    Measured: 24 months

  12. incidence of ECG abnormalities in Phase 1a combination with T-DM1

    Measured: 24 months

  13. Incidence of adverse events in Phase 1b monotherapy

    Measured: 24 months

  14. incidence of laboratory abnormalities in Phase 1b monotherapy

    Measured: 24 months

  15. incidence of ECG abnormalities in Phase 1b monotherapy

    Measured: 24 months

Secondary outcomes (10)

  1. Objective Response rate in Phase 1a monotherapy

    For patients with measurable disease at baseline, confirmed response per RECIST 1.1

    Measured: 24 months

  2. Objective response rate in Phase 1b monotherapy

    Confirmed response per RECIST 1.1

    Measured: 24 months

  3. Duration of response in Phase 1b monotherapy

    The time from the first response to progression or death per RECIST 1.1

    Measured: 24 months

  4. Brain metastases response in Phase 1b monotherapy

    for patients with measurable brain metastases at baseline, the percent of patients who have a confirmed response per RECIST 1.1

    Measured: 24 months

  5. PK parameter of area under the curve of ELVN-002 in Phase 1a monotherapy

    the concentration of ELVN-002 measured in the blood over 24 hours at steady state

    Measured: 21 days

  6. PK parameter of maximum concentration of ELVN-002 in Phase 1a monotherapy

    the maximum concentration of ELVN-002 measured in the blood at any time point at steady state

    Measured: 21 days

  7. PK parameter of terminal half life of ELVN-002 in Phase 1a monotherapy

    the half life of ELVN-002 calculated from the concentration of ELVN-002 in blood

    Measured: 21 days

  8. PK parameter of area under the curve of ELVN-002 in Phase 1b monotherapy

    the concentration of ELVN-002 measured in the blood over 24 hours at steady state

    Measured: 21 days

  9. PK parameter of maximum concentration of ELVN-002 in Phase 1b monotherapy

    the maximum concentration of ELVN-002 measured in the blood at any time point at steady state

    Measured: 21 days

  10. PK parameter of terminal half life of ELVN-002 in Phase 1b monotherapy

    the half life of ELVN-002 calculated from the concentration of ELVN-002 in blood

    Measured: 21 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Dec 2022
  2. Study start20 Mar 2023
  3. Primary completionJul 2026 (estimated)
  4. Study completionJul 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Phase 1 will be a dose escalation monotherapy according to the Bayesian Optimal Interval Design model Phase 1b will be a dose expansion: up to 40 patients randomized between 2 dose levels
Masking
None (open label)
Enrolment
198 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05650879
Sponsor's protocol ID
ELVN-002-001
Acronym
HER2
Status last verified
Jun 2025
First submitted
28 Nov 2022
Last updated
15 Jul 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ELVN-002, Fam-Trastuzumab Deruxtecan-Nxki and Trastuzumab emtansine in people with HER2 Mutant Non-small Cell Lung Cancer and HER2-positive Metastatic Breast Cancer, run by Enliven Therapeutics at 39 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 15 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 39 sites in Spain, France, Italy, South Korea, United States and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose limiting toxicities in Phase 1a monotherapy (time frame: 21 days). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05650879.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2025.

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